, RPX2003/RPX7009) tested against contemporary populations of gram-negative organisms, abstr 1615, Abstr. ID Week, 2012.

V. Cattoir, , 2004.

, Pathol. Biol. (Paris), vol.52, pp.607-623

M. Cecchini, P. Kolb, N. Majeux, and A. Caflisch, Automated docking of highly flexible ligands by genetic algorithms: A critical assessment, J. Comput. Chem, vol.25, pp.412-422, 2004.

R. Chakraborty, E. Storey, and D. Van-der-helm, Molecular mechanism of ferricsiderophore passage through the outer membrane receptor proteins of Escherichia coli, BioMetals, vol.20, pp.263-274, 2007.

C. Chen, J. Rahil, R. F. Pratt, and O. Herzberg, Structure of a Phosphonate-inhibited ?-Lactamase, J. Mol. Biol, vol.234, pp.165-178, 1993.

Y. Chen, Beware of docking!, Trends Pharmacol. Sci, vol.36, pp.78-95, 2015.

Y. Chen, A. Mcreynolds, and B. K. Shoichet, Re-examining the role of Lys67 in class C ?-lactamase catalysis, Protein Sci, vol.18, pp.662-671, 2009.

J. Chiou, S. Wan, K. Chan, P. So, D. He et al., Ebselen as a potent covalent inhibitor of New Delhi metallo-?-lactamase (NDM-1), Chem. Commun, vol.51, pp.9543-9546, 2015.

T. Christopeit, A. Albert, and H. Leiros, Discovery of a novel covalent non-?-lactam inhibitor of the metallo-?-lactamase NDM-1, Bioorg. Med. Chem, vol.24, pp.2947-2953, 2016.

N. O. Concha, C. A. Janson, P. Rowling, S. Pearson, C. A. Cheever et al., Crystal Structure of the IMP-1 Metallo ?-Lactamase from Pseudomonas aeruginosa and Its Complex with a Mercaptocarboxylate Inhibitor: Binding Determinants of a Potent, 2000.

N. O. Concha, B. A. Rasmussen, K. Bush, and O. Herzberg, Crystal structure of the wide-spectrum binuclear zinc ?-lactamase from Bacteroides fragilis, Structure, vol.4, pp.823-836, 1996.

R. A. Copeland, Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists, Methods Biochem. Anal, vol.46, pp.1-265, 2005.

J. L. Crandon and D. P. Nicolau, Vitro Activity of Cefepime/AAI101 and Comparators against Cefepime Non-susceptible Enterobacteriaceae. Pathog, vol.4, pp.620-625, 2015.

G. Crichlow, A. P. Kuzin, M. Nukaga, K. Mayama, T. Sawai et al., Structure of the extended-spectrum class C ?lactamase of Enterobacter cloacae GC1, a natural mutant with a tandem tripeptide insertion, Biochemistry, vol.38, pp.10256-61, 1999.

I. E. Crompton, B. K. Cuthbert, G. Lowe, and S. G. Waley, ?-lactamase inhibitors. The inhibition of serine ?-lactamases by specific boronic acids, Biochem. J, vol.251, pp.453-462, 1988.

M. W. Crowder, J. Spencer, and A. J. Vila, Metallo-?-lactamases: novel weaponry for antibiotic resistance in bacteria, Acc. Chem. Res, vol.39, pp.721-729, 2006.

M. W. Crowder, J. Spencer, and A. J. Vila, Metallo-?-lactamases: Novel Weaponry for Antibiotic Resistance in Bacteria, 2006.

N. A. Curtis, D. Orr, G. W. Ross, and M. G. Boulton, Affinities of penicillins and cephalosporins for the penicillin-binding proteins of Escherichia coli K-12 and their antibacterial activity, Antimicrob. Agents Chemother, vol.16, pp.533-542, 1979.

H. Daiyasu, K. Osaka, Y. Ishino, and H. Toh, Expansion of the zinc metallo-hydrolase family of the ?-lactamase fold, FEBS Lett, vol.503, pp.1-6, 2001.

J. Dobias, V. Dénervaud-tendon, L. Poirel, and P. Nordmann, Activity of the novel siderophore cephalosporin cefiderocol against multidrug-resistant Gram-negative pathogens, Eur. J. Clin. Microbiol. Infect. Dis, vol.36, pp.2319-2327, 2017.

J. Docquier, V. Calderone, D. Luca, F. Benvenuti, M. Giuliani et al., Crystal Structure of the OXA-48 ?-Lactamase Reveals Mechanistic Diversity among Class D Carbapenemases, Chem. Biol, vol.16, pp.540-547, 2009.

J. Docquier and S. Mangani, Structure-Function Relationships of Class D Carbapenemases, Curr. Drug Targets, vol.17, pp.1061-1071, 2016.

S. M. Drawz, M. Babic, C. R. Bethel, M. Taracila, A. M. Distler et al., Inhibition of the class C ?lactamase from Acinetobacter spp.: insights into effective inhibitor design, Biochemistry, vol.49, pp.329-369, 2010.

S. M. Drawz, M. Taracila, E. Caselli, F. Prati, and R. A. Bonomo, Exploring sequence requirements for C 3 /C 4 carboxylate recognition in the Pseudomonas aeruginosa cephalosporinase: Insights into plasticity of the AmpC ?-lactamase, Protein Sci, vol.20, pp.941-958, 2011.

S. M. Drawz, M. Taracila, E. Caselli, F. Prati, and R. A. Bonomo, Exploring sequence requirements for C?/C? carboxylate recognition in the Pseudomonas aeruginosa cephalosporinase: Insights into plasticity of the AmpC ?-lactamase, Protein Sci, vol.20, pp.941-58, 2011.

A. Dubus, S. Normark, M. Kania, and M. Page, Role of asparagine 152 in catalysis of ?-lactam hydrolysis by Escherichia coli AmpC ?-lactamase studied by site-directed mutagenesis, Biochemistry, vol.34, pp.7757-7764, 1995.

A. Dubus, S. Normark, M. Kania, and M. Page, The Role of Tyrosine 150 in Catalysis of ?-Lactam Hydrolysis by AmpC ?-Lactamase from Escherichia coli Investigated by Site-Directed Mutagenesis, Biochemistry, vol.33, pp.8577-8586, 1994.

T. F. Durand-réville, S. Guler, J. Comita-prevoir, B. Chen, N. Bifulco et al., ETX2514 is a broad-spectrum ?lactamase inhibitor for the treatment of drug-resistant Gram-negative bacteria including Acinetobacter baumannii, Nat. Microbiol, vol.2, p.17104, 2017.

C. De-duve and R. Wattiaux, Functions of lysosomes, Annu. Rev. Physiol, vol.28, pp.435-92, 1966.

D. E. Ehmann, H. Jahic, P. L. Ross, R. Gu, J. Hu et al., Kinetics of avibactam inhibition against Class A, C, and D ?-lactamases, J. Biol. Chem, vol.288, pp.27960-71, 2013.

D. E. Ehmann, H. Jahi?, P. L. Ross, R. Gu, J. Hu et al., Avibactam is a covalent, reversible, non-?lactam ?-lactamase inhibitor, Proc. Natl. Acad. Sci. U. S. A, vol.109, pp.11663-11671, 2012.

M. Ehrmann, The Periplasm, 2007.

O. Eidam, C. Romagnoli, E. Caselli, K. Babaoglu, D. T. Pohlhaus et al., Design, Synthesis, Crystal Structures, and Antimicrobial Activity of Sulfonamide Boronic Acids as ?-Lactamase Inhibitors, J. Med. Chem, vol.53, pp.7852-7863, 2010.

R. A. Engh and R. Huber, Structure quality and target parameters, International Tables for Crystallography, pp.382-392, 2006.

R. A. Engh, R. Huber, and . Iucr, Accurate bond and angle parameters for X-ray protein structure refinement, Acta Crystallogr. Sect. A Found. Crystallogr, vol.47, pp.392-400, 1991.

A. R. English, J. A. Retsema, A. E. Girard, J. E. Lynch, and W. E. Barth, CP-45,899, a ?-lactamase inhibitor that extends the antibacterial spectrum of ?-lactams: initial bacteriological characterization, Antimicrob. Agents Chemother, vol.14, pp.414-423, 1978.

M. C. Enright, D. A. Robinson, G. Randle, E. J. Feil, H. Grundmann et al., The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA), Proc. Natl. Acad. Sci. U. S. A, vol.99, pp.7687-92, 2002.

M. E. Falagas, T. Skalidis, K. Z. Vardakas, and N. J. Legakis, Activity of cefiderocol (S-649266) against carbapenem-resistant Gramnegative bacteria collected from inpatients in Greek hospitals, J. Antimicrob. Chemother, vol.72, pp.1704-1708, 2017.

S. B. Falconer, S. A. Reid-yu, A. M. King, S. S. Gehrke, W. Wang et al., Zinc Chelation by a Small-Molecule Adjuvant Potentiates Meropenem Activity in Vivo against NDM-1-Producing Klebsiella pneumoniae, ACS Infect. Dis, vol.1, pp.533-543, 2015.

J. Fisher, J. G. Belasco, R. L. Charnas, S. Khosla, and J. R. Knowles, ?-lactamase inactivation by mechanism-based reagents, Philos. Trans. R. Soc. Lond. B. Biol. Sci, vol.289, pp.309-328, 1980.

T. R. Fritsche, H. S. Sader, and R. N. Jones, Antimicrobial activity of ceftobiprole, a novel anti-methicillin-resistant Staphylococcus aureus cephalosporin, tested against contemporary pathogens: results from the SENTRY Antimicrobial Surveillance Program, Diagn. Microbiol. Infect. Dis, vol.61, pp.86-95, 2005.

M. Galleni and J. Frère, Kinetics of ?-Lactamases and Penicillin-Binding Proteins, Enzyme-Mediated Resistance to Antibiotics. American Society of Microbiology, pp.195-213, 2007.

M. Galleni, J. Lamotte-brasseur, G. M. Rossolini, J. Spencer, O. Dideberg et al., Standard numbering scheme for class B ?-lactamases, Antimicrob. Agents Chemother, vol.45, pp.660-663, 2001.

G. Garau, C. Bebrone, A. C. Galleni, M. Frère, J. Dideberg et al., A metallo-?-lactamase enzyme in action: crystal structures of the monozinc carbapenemase CphA and its complex with biapenem, J. Mol. Biol, vol.345, pp.785-95, 2005.

G. Garau, I. García-sáez, C. Bebrone, C. Anne, P. Mercuri et al., Update of the standard numbering scheme for class B ?-lactamases, Antimicrob. Agents Chemother, vol.48, pp.2347-2356, 2004.

I. Garcia-saez, J. Docquier, G. M. Rossolini, and O. Dideberg, The Three-Dimensional Structure of VIM-2, a Zn-?-Lactamase from Pseudomonas aeruginosa in Its Reduced and Oxidised Form, J. Mol. Biol, vol.375, pp.604-611, 2008.

I. García-saez, J. Hopkins, C. Papamicael, N. Franceschini, G. Amicosante et al., The 1.5-A structure of Chryseobacterium meningosepticum zinc ?-lactamase in complex with the inhibitor, Dcaptopril, J. Biol. Chem, vol.278, pp.23868-73, 2003.

I. Garc??a-sáez, P. Mercuri, C. Papamicael, R. Kahn, J. Frère et al., Three-dimensional Structure of FEZ-1, a Monomeric Subclass B3 Metallo-?-lactamase from Fluoribacter gormanii, in Native Form and in Complex with d-Captopril, J. Mol. Biol, vol.325, pp.651-660, 2003.

N. H. Georgopapadakou, S. A. Smith, C. M. Cimarusti, and R. B. Sykes, Binding of monobactams to penicillin-binding proteins of Escherichia coli and Staphylococcus aureus: relation to antibacterial activity, Antimicrob. Agents Chemother, vol.23, pp.98-104, 1983.

J. M. Ghuysen, Serine ?-Lactamases and Penicillin-Binding Proteins, Annu. Rev. Microbiol, vol.45, pp.37-67, 1991.

C. Goffin and J. M. Ghuysen, Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol, Mol. Biol. Rev, vol.62, pp.1079-93, 1998.

D. Golemi-kotra, S. O. Meroueh, C. Kim, S. B. Vakulenko, A. Bulychev et al., The Importance of a Critical Protonation State and the Fate of the Catalytic Steps in Class A ?-Lactamases and Penicillinbinding Proteins, J. Biol. Chem, vol.279, p.34665, 2004.

D. Golemi, L. Maveyraud, A. Ishiwata, S. Tranier, K. Miyashita et al., 6-(hydroxyalkyl)penicillanates as probes for mechanisms of ?-lactamases, J. Antibiot. (Tokyo), vol.53, pp.1022-1029, 2000.

L. J. González, D. M. Moreno, R. A. Bonomo, and A. J. Vila, Host-Specific Enzyme-Substrate Interactions in SPM-1 Metallo-?-Lactamase Are Modulated by Second Sphere Residues, PLoS Pathog, vol.10, p.1003817, 2014.

M. M. González, M. Kosmopoulou, M. F. Mojica, V. Castillo, P. Hinchliffe et al., Bisthiazolidines: A Substrate-Mimicking Scaffold as an Inhibitor of the NDM-1 Carbapenemase, ACS Infect. Dis, vol.1, pp.544-554, 2015.

I. M. Gould, M. Z. David, S. Esposito, J. Garau, G. Lina et al., New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance, Int. J. Antimicrob. Agents, vol.39, pp.96-104, 2012.

D. C. Griffith, J. S. Loutit, E. E. Morgan, S. Durso, and M. N. Dudley, Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of the ?-Lactamase Inhibitor Vaborbactam (RPX7009) in Healthy Adult Subjects, Antimicrob. Agents Chemother, vol.60, pp.6326-6358, 2016.

I. Halperin, B. Ma, H. Wolfson, and R. Nussinov, Principles of docking: An overview of search algorithms and a guide to scoring functions, Proteins, vol.47, pp.409-452, 2002.

H. Hanberger, L. E. Nilsson, E. Svensson, and R. Maller, Synergic post-antibiotic effect of mecillinam, in combination with other ?-lactam antibiotics in relation to morphology and initial killing, J. Antimicrob. Chemother, vol.28, pp.523-555, 1991.

S. Hecker, K. Reddy, M. Totrov, G. Hirst, M. Sabet et al., Discovery of RPX7009, a broad-spectrum ?lactamase inhibitor with utility vs. class A serine carbapenemase, abstr F-848, In: Abstr. Intersci. Conf. Antimicrob. Agents Chemother, 2012.

S. J. Hecker, K. R. Reddy, M. Totrov, G. C. Hirst, O. Lomovskaya et al., Discovery of a Cyclic Boronic Acid ?-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases, J. Med. Chem, vol.58, pp.3682-3692, 2015.

W. A. Hendrickson, Stereochemically restrained refinement of macromolecular structures, Methods Enzymol, vol.115, pp.252-70, 1985.

M. Hernandez-valladares, A. Felici, G. Weber, H. W. Adolph, M. Zeppezauer et al., Zn(II) dependence of the Aeromonas hydrophila AE036 metallo-?-lactamase activity and stability, Biochemistry, vol.36, pp.11534-11575, 1997.

R. A. Hickman, D. Hughes, T. Cars, C. Malmberg, and O. Cars, Cell-wall-inhibiting antibiotic combinations with activity against multidrug-resistant Klebsiella pneumoniae and Escherichia coli, Clin. Microbiol. Infect, vol.20, pp.267-73, 2014.

P. G. Higgins, D. Stefanik, M. Page, M. Hackel, and H. Seifert, In vitro activity of the siderophore monosulfactam BAL30072 against meropenem-non-susceptible Acinetobacter baumannii, J. Antimicrob. Chemother, vol.67, pp.1167-1169, 2012.

P. G. Higgins, H. Wisplinghoff, D. Stefanik, and H. Seifert, In vitro activities of the ?-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam alone or in combination with ?-lactams against epidemiologically characterized multidrugresistant Acinetobacter baumannii strains, Antimicrob. Agents Chemother, vol.48, pp.1586-92, 2004.

Y. Hiraiwa, J. Saito, T. Watanabe, M. Yamada, A. Morinaka et al., X-ray crystallographic analysis of IMP-1 metallo-?-lactamase complexed with a 3-aminophthalic acid derivative, structure-based drug design, and synthesis of 3,6-disubstituted phthalic acid derivative inhibitors, Bioorg. Med. Chem. Lett, vol.24, pp.4891-4894, 2014.

H. L. Hirsh and H. F. Dowling, The treatment of Streptococcus viridans endocarditis with penicillin, South. Med. J, vol.39, pp.55-60, 1946.

B. Hofer, C. Dantier, K. Gebhardt, E. Desarbre, A. Schmitt-hoffmann et al., Combined effects of the siderophore monosulfactam BAL30072 and carbapenems on multidrug-resistant Gram-negative bacilli, J. Antimicrob. Chemother, vol.68, pp.1120-1129, 2013.

J. V. Höltje, Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli. Microbiol, Mol. Biol. Rev, vol.62, pp.181-203, 1998.

D. Huang and A. Caflisch, Library screening by fragment-based docking, J. Mol. Recognit, vol.23, 2009.

D. Huang, E. Rossini, S. Steiner, and A. Caflisch, Structured Water Molecules in the Binding Site of Bromodomains Can Be Displaced by Cosolvent, ChemMedChem, vol.9, pp.573-579, 2014.

J. Huntley, W. Fast, S. J. Benkovic, P. E. Wright, and H. J. Dyson, Role of a solvent-exposed tryptophan in the recognition and binding of antibiotic substrates for a metallo-?-lactamase, Protein Sci, vol.12, pp.1368-1375, 2003.

J. Huntley, S. Scrofani, M. J. Osborne, P. E. Wright, and D. H. Jane, Dynamics of the Metallo-?-Lactamase from Bacteroides fragilis in the Presence and Absence of a Tight-Binding Inhibitor, 2000.

U. Imtiaz, E. M. Billings, J. R. Knox, and S. Mobashery, A structure-based analysis of the inhibition of class A ?-lactamases by sulbactam, Biochemistry, vol.33, pp.5728-5766, 1994.

U. Imtiaz, E. K. Manavathu, S. A. Lerner, and S. Mobashery, Critical hydrogen bonding by serine 235 for cephalosporinase activity of TEM-1 ?-lactamase, Antimicrob. Agents Chemother, vol.37, pp.2438-2480, 1993.

T. Ito-horiyama, Y. Ishii, A. Ito, T. Sato, R. Nakamura et al., Stability of Novel Siderophore Cephalosporin S-649266 against Clinically Relevant Carbapenemases, Antimicrob. Agents Chemother, vol.60, pp.4384-4390, 2016.

A. Ito, N. Kohira, S. K. Bouchillon, J. West, S. Rittenhouse et al., In vitro antimicrobial activity of S-649266, a catechol-substituted siderophore cephalosporin, when tested against non-fermenting Gram-negative bacteria, J. Antimicrob. Chemother, vol.71, pp.670-677, 2016.

A. Ito, T. Nishikawa, S. Matsumoto, H. Yoshizawa, T. Sato et al., Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa, Antimicrob. Agents Chemother, vol.60, pp.7396-7401, 2016.

M. Jaskolski, M. Gilski, Z. Dauter, and A. Wlodawer, Stereochemical restraints revisited: how accurate are refinement targets and how much should protein structures be allowed to deviate from them?, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.63, pp.611-620, 2007.

G. Jones, P. Willett, R. C. Glen, A. R. Leach, and R. Taylor, Development and validation of a genetic algorithm for flexible docking, J. Mol. Biol, vol.267, pp.727-748, 1997.

F. M. Kahan, H. Kropp, J. G. Sundelof, and J. Birnbaum, Thienamycin: development of imipenen-cilastatin, J. Antimicrob. Chemother, vol.12, 1983.

J. S. Kahan, F. M. Kahan, R. Goegelman, S. A. Currie, M. Jackson et al., Thienamycin, a new ?-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties, J. Antibiot. (Tokyo), vol.32, pp.1-12, 1979.

Y. Kamio and H. Nikaido, Outer membrane of Salmonella typhimurium: accessibility of phospholipid head groups to phospholipase c and cyanogen bromide activated dextran in the external medium, Biochemistry, vol.15, pp.2561-70, 1976.

M. Karplus and J. A. Mccammon, Molecular dynamics simulations of biomolecules, Nat. Struct. Biol, vol.9, pp.646-52, 2002.

W. Ke, J. M. Sampson, C. Ori, F. Prati, S. M. Drawz et al., Novel Insights into the Mode of Inhibition of Class A SHV-1 ?-Lactamases Revealed by Boronic Acid Transition State Inhibitors, Antimicrob. Agents Chemother, vol.55, pp.174-183, 2011.

Y. Kim, C. Tesar, J. Mire, R. Jedrzejczak, A. Binkowski et al., Structure of Apo-and Monometalated Forms of NDM-1-A Highly Potent Carbapenem-Hydrolyzing Metallo-?-Lactamase, PLoS One, vol.6, p.24621, 2011.

A. M. King, S. A. Reid-yu, W. W. King, D. T. , D. Pascale et al., Aspergillomarasmine A overcomes metallo-?-lactamase antibiotic resistance, Nature, vol.510, pp.503-506, 2014.

D. King and N. Strynadka, Crystal structure of New Delhi metallo-?-lactamase reveals molecular basis for antibiotic resistance, Protein Sci, vol.20, pp.1484-1491, 2011.

D. T. King, L. J. Worrall, R. Gruninger, and N. Strynadka, New Delhi Metallo-?-Lactamase: Structural Insights into ?-Lactam Recognition and Inhibition, J. Am. Chem. Soc, vol.134, pp.11362-11365, 2012.

G. J. Kleywegt and T. A. Jones, Where freedom is given, liberties are taken, Structure, vol.3, pp.535-575, 1995.

F. Klingler, T. A. Wichelhaus, D. Frank, J. Cuesta-bernal, J. El-delik et al., Approved Drugs Containing Thiols as Inhibitors of Metallo-?-lactamases: Strategy To Combat Multidrug-Resistant Bacteria, J. Med. Chem, vol.58, pp.3626-3630, 2015.

N. Kohira, J. West, A. Ito, T. Ito-horiyama, R. Nakamura et al., S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains, In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, vol.60, pp.729-763, 2016.

P. Kolb, R. S. Ferreira, J. J. Irwin, and B. K. Shoichet, Docking and chemoinformatic screens for new ligands and targets, Curr. Opin. Biotechnol, vol.20, pp.429-465, 2009.

N. P. Krishnan, N. Q. Nguyen, K. M. Papp-wallace, R. A. Bonomo, and F. Van-den-akker, Inhibition of Klebsiella ?-Lactamases (SHV-1 and KPC-2) by Avibactam: A Structural Study, PLoS One, vol.10, p.136813, 2015.

H. Kropp, J. G. Sundelof, R. Hajdu, and F. M. Kahan, Metabolism of thienamycin and related carbapenem antibiotics by the renal dipeptidase, dehydropeptidase, Antimicrob. Agents Chemother, vol.22, pp.62-70, 1982.

S. D. Lahiri, S. Mangani, T. Durand-reville, M. Benvenuti, D. Luca et al., Structural Insight into Potent Broad-Spectrum Inhibition with Reversible Recyclization Mechanism: Avibactam in Complex with CTX-M-15 and Pseudomonas aeruginosa AmpC ?-Lactamases, Antimicrob. Agents Chemother, vol.57, pp.2496-2505, 2013.

S. D. Lahiri, S. Mangani, H. Jahi?, M. Benvenuti, T. F. Durand-reville et al., Molecular basis of selective inhibition and slow reversibility of avibactam against class D carbapenemases: a structure-guided study of OXA-24 and OXA-48, ACS Chem. Biol, vol.10, pp.591-600, 2015.

P. Lambert, Bacterial resistance to antibiotics: Modified target sites, Adv. Drug Deliv. Rev, vol.57, pp.1471-1485, 2005.

M. A. Larkin, G. Blackshields, N. P. Brown, R. Chenna, P. A. Mcgettigan et al., Clustal W and Clustal X version 2.0, Bioinformatics, vol.23, pp.2947-2948, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00206210

P. Lassaux, D. Traoré, E. Loisel, A. Favier, J. Docquier et al., Biochemical and structural characterization of the subclass B1 metallo-?-lactamase VIM-4, Antimicrob. Agents Chemother, vol.55, pp.1248-55, 2011.

P. Lavanya, S. Ramaiah, and A. Anbarasu, A Molecular Docking and Dynamics Study to Screen Potent Anti-Staphylococcal Compounds Against Ceftaroline Resistant MRSA, J. Cell. Biochem, vol.117, pp.542-548, 2016.

A. S. Levin, Multiresistant Acinetobacter infections: a role for sulbactam combinations in overcoming an emerging worldwide problem, Clin. Microbiol. Infect, vol.8, pp.144-53, 2002.

N. Li and R. F. Pratt, Inhibition of Serine ?-Lactamases by Acyl Phosph(on)ates: A New Source of Inert Acyl, 1998.

X. Li and H. Nikaido, Efflux-mediated drug resistance in bacteria: an update, Drugs, vol.69, pp.1555-623, 2009.

B. Liénard, G. Garau, L. Horsfall, A. I. Karsisiotis, C. Damblon et al., Structural basis for the broad-spectrum inhibition of metallo-?-lactamases by thiols, Org. Biomol. Chem, vol.6, p.2282, 2008.

K. Lindorff-larsen, P. Maragakis, S. Piana, M. P. Eastwood, R. O. Dror et al., Systematic Validation of Protein Force Fields against Experimental Data, PLoS One, vol.7, p.32131, 2012.

R. N. Lindquist and C. Terry, Inhibition of subtilisin by boronic acids, potential analogs of tetrahedral reaction intermediates, Arch. Biochem. Biophys, vol.160, pp.135-179, 1974.

X. Liu, Y. Shi, J. S. Kang, P. Oelschlaeger, and K. Yang, Amino Acid Thioester Derivatives: A Highly Promising Scaffold for the Development of Metallo-?-lactamase L1 Inhibitors, ACS Med. Chem. Lett, vol.6, pp.660-664, 2015.

D. Livermore, S. Mushtaq, and H. D. , Activity of RPX2003 -RPX7009 combinations against carbapenem-resistant Enterobacteriaceae, abstr F-853, Abstr. Intersci. Conf. Antimicrob. Agents Chemother, 2012.

D. M. Livermore, S. Mushtaq, M. Warner, C. Miossec, and N. Woodford, NXL104 combinations versus Enterobacteriaceae with CTX-M extended-spectrum ?-lactamases and carbapenemases, J. Antimicrob. Chemother, vol.62, pp.1053-1059, 2008.

D. M. Livermore, M. Warner, S. Mushtaq, and N. Woodford, Interactions of OP0595, a Novel Triple-Action Diazabicyclooctane, with ?-Lactams against OP0595-Resistant Enterobacteriaceae Mutants, Antimicrob. Agents Chemother, vol.60, pp.554-560, 2016.

E. Lobkovsky, P. C. Moews, H. Liu, H. Zhao, J. M. Frere et al., Evolution of an enzyme activity: crystallographic structure at 2-A resolution of cephalosporinase from the ampC gene of Enterobacter cloacae P99 and comparison with a class A penicillinase, Proc. Natl. Acad. Sci. U. S. A, vol.90, pp.11257-61, 1993.

A. E. Lohning, S. M. Levonis, B. Williams-noonan, and S. S. Schweiker, A Practical Guide to Molecular Docking and Homology Modelling for Medicinal Chemists, Curr. Top. Med. Chem, vol.17, 2017.

O. Lomovskaya, D. Rubio-aparicio, D. Sun, D. Griffith, and M. N. Dudley, Microbiological characterization of novel broadspectrum inhibitors of serine and metallo carbapenemases, anstr F-264, Abstr. Intersci. Conf. Antimicrob. Agents Chemother, 2015.

F. De-luca, M. Benvenuti, F. Carboni, C. Pozzi, G. M. Rossolini et al., Evolution to carbapenemhydrolyzing activity in noncarbapenemase class D ?-lactamase OXA-10 by rational protein design, Proc. Natl. Acad. Sci. U. S. A, vol.108, pp.18424-18433, 2011.

B. A. Lund, T. Christopeit, Y. Guttormsen, A. Bayer, and H. Leiros, Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening, J. Med. Chem, vol.59, pp.5542-54, 2016.

M. Madigan, Brock biology of microorganisms, 2017.

S. Majumdar, S. A. Adediran, M. Nukaga, and R. F. Pratt, Inhibition of class D ?-lactamases by diaroyl phosphates, Biochemistry, vol.44, pp.16121-16130, 2005.

S. Majumdar and R. F. Pratt, Inhibition of Class A and C ?-Lactamases by Diaroyl Phosphates, Biochemistry, vol.48, pp.8285-8292, 2009.

K. Malathi and S. Ramaiah, Bioinformatics approaches for new drug discovery: a review, Biotechnol. Genet. Eng. Rev, vol.34, pp.243-260, 2018.

K. Malathi and S. Ramaiah, Bioinformatics approaches for new drug discovery: a review, Biotechnol. Genet. Eng. Rev, vol.34, pp.243-260, 2018.

K. Malathi and S. Ramaiah, Molecular Docking and Molecular Dynamics Studies to Identify Potential OXA-10 Extended Spectrum ?-Lactamase Non-hydrolysing Inhibitors for Pseudomonas aeruginosa, Cell Biochem. Biophys, vol.74, pp.141-55, 2016.

S. Mariotte-boyer, M. H. Nicolas-chanoine, and R. Labia, A kinetic study of NMC-A ?-lactamase, an Ambler class A carbapenemase also hydrolyzing cephamycins, FEMS Microbiol. Lett, vol.143, pp.29-33, 1996.

J. Martinez-beltran, E. Loza, A. Gomez-alferez, J. Romero-vivas, and E. Bouza, Temocillin. Drugs, vol.29, pp.91-97, 1985.

L. Martínez-martínez, Extended-spectrum ?-lactamases and the permeability barrier, Clin. Microbiol. Infect, vol.14, pp.82-89, 2008.

I. Massova and S. Mobashery, Kinship and diversification of bacterial penicillin-binding proteins and ?-lactamases, Antimicrob. Agents Chemother, vol.42, pp.1-17, 1998.

L. Maveyraud, D. Golemi-kotra, A. Ishiwata, O. Meroueh, S. Mobashery et al., High-resolution X-ray structure of an acyl-enzyme species for the class D OXA-10 ?-lactamase, J. Am. Chem. Soc, vol.124, pp.2461-2466, 2002.

M. Meini, L. Llarrull, A. Vila, M. Meini, L. I. Llarrull et al., Evolution of Metallo-?-lactamases: Trends Revealed by Natural Diversity and in vitro Evolution, Antibiotics, vol.3, pp.285-316, 2014.

C. Michaux, P. Charlier, J. Frère, and J. Wouters, Crystal Structure of BRL 42715, C6-( N 1-Methyl-1,2,3-triazolylmethylene)penem, in Complex with Enterobacter c loacae 908R ?-Lactamase: Evidence for a Stereoselective Mechanism from Docking Studies, J. Am. Chem. Soc, vol.127, pp.3262-3263, 2005.

J. M. Miller, C. N. Baker, and C. Thornsberry, Inhibition of ?-lactamase in Neisseria gonorrhoeae by sodium clavulanate, Antimicrob. Agents Chemother, vol.14, pp.794-800, 1978.

G. Minasov, X. Wang, and B. K. Shoichet, An Ultrahigh Resolution Structure of TEM-1 ?-Lactamase Suggests a Role for Glu166 as the General Base in Acylation, J. Am. Chem. Soc, vol.124, pp.5333-5340, 2002.

J. M. Mitchell, J. R. Clasman, C. M. June, K. Kaitany, J. R. Lafleur et al., Structural Basis of Activity against Aztreonam and Extended Spectrum Cephalosporins for Two Carbapenem-Hydrolyzing Class D ?-Lactamases from Acinetobacter baumannii, Biochemistry, vol.54, pp.1976-1987, 2015.

P. Mitchell, Approaches to the analysis of specific membrane transport, Biol. Struct. Funct, vol.2, pp.581-599, 1961.

M. F. Mojica, S. G. Mahler, C. R. Bethel, M. A. Taracila, M. Kosmopoulou et al., Exploring the Role of Residue 228 in Substrate and Inhibitor Recognition by VIM Metallo-?-lactamases, Biochemistry, vol.54, pp.3183-3196, 2015.

D. Monnaie, A. Dubus, D. Cooke, J. Marchand-brynaert, S. Normark et al., Role of Residue Lys315 in the Mechanism of Action of the Enterobacter cloacae 908R ?-Lactamase, Biochemistry, vol.33, pp.5193-5201, 1994.

D. Monnaie, A. Dubus, and J. M. Frère, The role of lysine-67 in a class C ?-lactamase is mainly electrostatic, Biochem. J, vol.302, pp.1-4, 1994.

A. Morinaka, Y. Tsutsumi, M. Yamada, K. Suzuki, T. Watanabe et al., OP0595, a new diazabicyclooctane: mode of action as a serine ?-lactamase inhibitor, antibiotic and ?-lactam "enhancer, J. Antimicrob. Chemother, vol.70, pp.2779-86, 2015.

G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew et al., AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, J. Comput. Chem, vol.30, pp.2785-2791, 2009.

B. Moya, I. M. Barcelo, S. Bhagwat, M. Patel, G. Bou et al., WCK 5107 (Zidebactam) and WCK 5153 Are Novel Inhibitors of PBP2 Showing Potent "?-Lactam Enhancer" Activity against Pseudomonas aeruginosa, Including Multidrug-Resistant Metallo-?-Lactamase-Producing High-Risk Clones, Antimicrob. Agents Chemother, p.61, 2017.

L. Moynié, A. Luscher, D. Rolo, D. Pletzer, A. Tortajada et al., Structure and Function of the PiuA and PirA Siderophore-Drug Receptors from Pseudomonas aeruginosa and Acinetobacter baumannii, Antimicrob. Agents Chemother, vol.61, pp.2531-2547, 2017.

C. W. Mullineaux, A. Nenninger, N. Ray, and C. Robinson, Diffusion of green fluorescent protein in three cell environments in Escherichia coli, J. Bacteriol, vol.188, pp.3442-3450, 2006.

A. G. Murzin, S. E. Brenner, T. Hubbard, and C. Chothia, SCOP: A structural classification of proteins database for the investigation of sequences and structures, J. Mol. Biol, vol.247, pp.536-540, 1995.

S. Mushtaq, M. Warner, G. Williams, I. Critchley, and D. M. Livermore, Activity of chequerboard combinations of ceftaroline and NXL104 versus ?-lactamase-producing Enterobacteriaceae, J. Antimicrob. Chemother, vol.65, pp.1428-1432, 2010.

S. Mushtaq, N. Woodford, R. Hope, R. Adkin, and D. M. Livermore, Activity of BAL30072 alone or combined with ?-lactamase inhibitors or with meropenem against carbapenem-resistant Enterobacteriaceae and non-fermenters, J. Antimicrob. Chemother, vol.68, pp.1601-1608, 2013.

T. Naas, L. Dortet, and B. I. Iorga, Structural and Functional Aspects of Class A Carbapenemases, Curr. Drug Targets, vol.17, pp.1006-1034, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02135284

T. Naas, L. Vandel, W. Sougakoff, D. M. Livermore, and P. Nordmann, Cloning and sequence analysis of the gene for a carbapenem-hydrolyzing class A ?-lactamase, Sme-1, from Serratia marcescens S6, Antimicrob. Agents Chemother, vol.38, pp.1262-70, 1994.

L. Nauton, R. Kahn, G. Garau, J. F. Hernandez, and O. Dideberg, Structural Insights into the Design of Inhibitors for the L1 Metallo-?-lactamase from Stenotrophomonas maltophilia, J. Mol. Biol, vol.375, pp.257-269, 2008.

H. C. Neu and K. P. Fu, Clavulanic acid, a novel inhibitor of ?-lactamases, Antimicrob. Agents Chemother, vol.14, pp.650-655, 1978.

G. G. Newton and E. P. Abraham, Cephalosporin C, a new antibiotic containing sulphur and D-alpha-aminoadipic acid, Nature, vol.175, p.548, 1955.

H. Nikaido, Molecular basis of bacterial outer membrane permeability revisited. Microbiol, Mol. Biol. Rev, vol.67, pp.593-656, 2003.

P. Nordmann, L. Dortet, and L. Poirel, Carbapenem resistance in Enterobacteriaceae: here is the storm!, Trends Mol. Med, vol.18, pp.263-272, 2012.

E. O'neill, H. Humphreys, J. Phillips, and E. G. Smyth, Third-generation cephalosporin resistance among Gram-negative bacilli causing meningitis in neurosurgical patients: significant challenges in ensuring effective antibiotic therapy, J. Antimicrob. Chemother, vol.57, pp.356-359, 2006.

M. Page, Siderophore conjugates, Ann. N. Y. Acad. Sci, vol.1277, pp.115-126, 2013.

M. Page, C. Dantier, E. Desarbre, B. Gaucher, K. Gebhardt et al., In vitro and in vivo properties of BAL30376, a ?-lactam and dual beta-lactamase inhibitor combination with enhanced activity against Gram-negative Bacilli that express multiple ?-lactamases, Antimicrob. Agents Chemother, vol.55, pp.1510-1519, 2011.

J. Painter and E. A. Merritt, Optimal description of a protein structure in terms of multiple groups undergoing TLS motion, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.62, pp.439-450, 2006.

A. R. Palacios, M. F. Mojica, E. Giannini, M. A. Taracila, C. R. Bethel et al., THE REACTION MECHANISM OF METALLO-?-LACTAMASES IS TUNED BY THE CONFORMATION OF AN ACTIVE SITE MOBILE LOOP, Antimicrob. Agents Chemother, pp.1754-1772, 2018.

T. Palzkill, Metallo-?-lactamase structure and function, Ann. N. Y. Acad. Sci, vol.1277, pp.91-104, 2013.

J. T. Park and J. L. Strominger, Mode of action of penicillin, Science, vol.125, pp.99-101, 1957.

P. Pattanaik, C. R. Bethel, A. M. Hujer, K. M. Hujer, A. M. Distler et al., Strategic design of an effective beta-lactamase inhibitor: LN-1-255, a 6-alkylidene-2'-substituted penicillin sulfone, J. Biol. Chem, vol.284, pp.945-53, 2009.

R. Paul-soto, R. Bauer, J. M. Frère, M. Galleni, W. Meyer-klaucke et al., Mono-and binuclear Zn2+-?-lactamase. Role of the conserved cysteine in the catalytic mechanism, J. Biol. Chem, vol.274, pp.13242-13251, 1999.

R. Paul-soto, R. Bauer, J. M. Frère, M. Galleni, W. Meyer-klaucke et al., Mono-and binuclear Zn2+-?-lactamase. Role of the conserved cysteine in the catalytic mechanism, J. Biol. Chem, vol.274, pp.13242-13251, 1999.

A. Pottegård, A. Broe, R. Aabenhus, L. Bjerrum, J. Hallas et al., Use of Antibiotics in Children, Pediatr. Infect. Dis. J, vol.34, pp.16-22, 2015.

R. A. Powers, Structural and Functional Aspects of Extended-Spectrum AmpC Cephalosporinases, Curr. Drug Targets, vol.17, pp.1051-60, 2016.

R. A. Powers, F. Morandi, and B. K. Shoichet, Structure-based discovery of a novel, noncovalent inhibitor of AmpC ?-lactamase, Structure, vol.10, pp.1013-1036, 2002.

R. A. Powers and B. K. Shoichet, Structure-Based Approach for Binding Site Identification on AmpC ?-Lactamase, 2002.

R. F. Pratt, Inhibition of a class C ?-lactamase by a specific phosphonate monoester, Science, vol.246, pp.917-926, 1989.

C. R. Raetz and W. Dowhan, Biosynthesis and function of phospholipids in Escherichia coli, Annu. Rev. Biochem, vol.265, pp.635-700, 1990.

C. H. Rammelkamp and C. S. Keefer, Penicillin: its antibacterial effect in whole blood and serum for the hemolytic Streptococcus and Staphylococcus aureus, J. Clin. Invest, vol.22, pp.649-657, 1943.

R. M. Rasia and A. J. Vila, Exploring the Role and the Binding Affinity of a Second Zinc Equivalent in B. cereus Metallo-?lactamase, 2002.

B. A. Rasmussen, K. Bush, D. Keeney, Y. Yang, R. Hare et al., Characterization of IMI-1 ?-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae, Antimicrob. Agents Chemother, vol.40, pp.2080-2086, 1996.

C. Reading and M. Cole, Clavulanic acid: a ?-lactamase-inhiting beta-lactam from Streptomyces clavuligerus, Antimicrob. Agents Chemother, vol.11, pp.852-859, 1977.

H. Richter, P. Angehrn, C. Hubschwerlen, K. M. Page, M. Specklin et al., Design, Synthesis, and Evaluation of 2?-Alkenyl Penam Sulfone Acids as Inhibitors of ?-Lactamases, 1996.

X. Robert and P. Gouet, Deciphering key features in protein structures with the new ENDscript server, Nucleic Acids Res, vol.42, pp.320-324, 2014.

A. Rojas, T. Ganesh, Z. Manji, T. O'neill, and R. Dingledine, Inhibition of the prostaglandin E2 receptor EP2 prevents status epilepticus-induced deficits in the novel object recognition task in rats, Neuropharmacology, vol.110, pp.419-430, 2016.

P. A. Ropp, M. Hu, M. Olesky, and R. A. Nicholas, Mutations in ponA, the gene encoding penicillin-binding protein 1, and a novel locus, penC, are required for high-level chromosomally mediated penicillin resistance in Neisseria gonorrhoeae, Antimicrob. Agents Chemother, vol.46, pp.769-77, 2002.

A. Roy, P. R. Mcdonald, S. Sittampalam, and R. Chaguturu, Open access high throughput drug discovery in the public domain: a Mount Everest in the making, Curr. Pharm. Biotechnol, vol.11, pp.764-78, 2010.

S. Ruiz-carmona, D. Alvarez-garcia, N. Foloppe, A. B. Garmendia-doval, S. Juhos et al., rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids, PLoS Comput. Biol, vol.10, p.1003571, 2014.

A. M. Rydzik, J. Brem, S. S. Van-berkel, I. Pfeffer, A. Makena et al., Monitoring Conformational Changes in the NDM-1 Metallo-?-lactamase by 19 F NMR Spectroscopy, Angew. Chemie Int. Ed, vol.53, pp.3129-3133, 2014.

M. Sabet, Z. Tarazi, O. Lomovskaya, S. Hecke, M. Dudley et al., In vivo efficacy of the ?-lactamase inhibitor RPX7009 combined with the carbapenem RPX2003 against KPC-producing K. pneumoniae, abstr F-858, Abstr. Intersci. Conf. Antimicrob. Agents Chemother, 2012.

V. P. Sandanayaka, G. B. Feigelson, A. S. Prashad, Y. Yang, and P. J. Petersen, Allyl and propargyl substituted penam sulfones as versatile intermediates toward the syntheses of new ?-lactamase inhibitors, Bioorg. Med. Chem. Lett, vol.11, pp.997-1000, 2001.

V. P. Sandanayaka and Y. Yang, Dipolar Cycloaddition of Novel 6-(Nitrileoxidomethyl) Penam Sulfone: An Efficient Route to a New Class of ?-Lactamase Inhibitors, Org. Lett, vol.2, pp.3087-3090, 2000.

K. Sankaran and H. C. Wu, Lipid modification of bacterial prolipoprotein. Transfer of diacylglyceryl moiety from phosphatidylglycerol, J. Biol. Chem, vol.269, pp.19701-19707, 1994.

E. Sauvage, F. Kerff, M. Terrak, J. A. Ayala, and P. Charlier, The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis, FEMS Microbiol. Rev, vol.32, pp.234-258, 2008.

K. D. Schneider, C. R. Bethel, A. M. Distler, A. M. Hujer, R. A. Bonomo et al., Mutation of the Active Site Carboxy-Lysine (K70) of OXA-1 ?-Lactamase Results in a Deacylation-Deficient Enzyme, Biochemistry, vol.48, pp.6136-6145, 2009.

L. J. Scott, Ceftolozane/Tazobactam: A Review in Complicated Intra-Abdominal and Urinary Tract Infections, Drugs, vol.76, pp.231-242, 2016.

S. Scrofani, J. Chung, J. Huntley, S. J. Benkovic, P. E. Wright et al., NMR Characterization of the Metallo-?-lactamase from Bacteroides fragilis and Its Interaction with a Tight-Binding Inhibitor: Role of an Active-Site Loop, 1999.

H. M. Senn and W. Thiel, QM/MM methods for biomolecular systems, Angew. Chem. Int. Ed. Engl, vol.48, pp.1198-229, 2009.

D. De-seny, U. Heinz, S. Wommer, M. Kiefer, W. Meyer-klaucke et al., Metal ion binding and coordination geometry for wild type and mutants of metallo-?-lactamase from Bacillus cereus 569/H/9 (BcII): a combined thermodynamic, kinetic, and spectroscopic approach, J. Biol. Chem, vol.276, pp.45065-78, 2001.

L. Sevaille, L. Gavara, C. Bebrone, D. Luca, F. Nauton et al., ,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-?-lactamases, ChemMedChem, vol.12, pp.972-985, 2002.

J. Sgrignani, D. Luca, F. Torosyan, H. Docquier, J. Duan et al., Structure-based approach for identification of novel phenylboronic acids as serine-?-lactamase inhibitors, J. Comput. Aided. Mol. Des, vol.30, pp.851-861, 2016.

J. Sgrignani, B. Novati, G. Colombo, and G. Grazioso, Covalent docking of selected boron-based serine ?-lactamase inhibitors, J. Comput. Aided. Mol. Des, vol.29, pp.441-50, 2015.

A. B. Shapiro, N. Gao, H. Jahi?, N. M. Carter, A. Chen et al., Reversibility of Covalent, Broad-Spectrum Serine ?-Lactamase Inhibition by the Diazabicyclooctenone ETX2514, ACS Infect. Dis, vol.3, pp.833-844, 2017.

P. ?led? and A. Caflisch, Protein structure-based drug design: from docking to molecular dynamics, Curr. Opin. Struct. Biol, vol.48, pp.93-102, 2018.

C. Sotriffer, Docking of Covalent Ligands: Challenges and Approaches, Mol. Inform, vol.37, p.1800062, 2018.

D. Spiliotopoulos and A. Caflisch, Fragment-based in silico screening of bromodomain ligands, Drug Discov. Today Technol, vol.19, pp.81-90, 2016.

B. Spratt, L. Bowler, Q. Zhang, J. Zhou, and J. Smith, Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species, J. Mol. Evol, vol.34, pp.115-125, 1992.

B. G. Spratt, Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae, Nature, vol.332, pp.173-179, 1988.

B. G. Spratt, Q. Y. Zhang, D. M. Jones, A. Hutchison, J. A. Brannigan et al., Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis, Proc. Natl. Acad. Sci. U. S. A, vol.86, pp.8988-92, 1989.

B. G. Spratt, J. Zhou, M. Taylor, and M. J. Merrick, Monofunctional biosynthetic peptidoglycan transglycosylases, Mol. Microbiol, vol.19, pp.639-679, 1996.

T. Stachyra, P. Levasseur, M. Péchereau, A. Girard, M. Claudon et al., In vitro activity of the ?lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases, J. Antimicrob. Chemother, vol.64, pp.326-335, 2009.

T. Steinbrecher and A. Labahn, Towards accurate free energy calculations in ligand protein-binding studies, Curr. Med. Chem, vol.17, pp.767-85, 2010.

Y. Sumita and M. Fukasawa, Potent activity of meropenem against Escherichia coli arising from its simultaneous binding to penicillin-binding proteins 2 and 3, J. Antimicrob. Chemother, vol.36, pp.53-64, 1995.

R. B. Sykes, D. P. Bonner, K. Bush, and N. H. Georgopapadakou, Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria, Antimicrob. Agents Chemother, vol.21, pp.85-92, 1982.

P. K. Thakur, J. Kumar, D. Ray, F. Anjum, and M. I. Hassan, Search of potential inhibitor against New Delhi metallo-?-lactamase 1 from a series of antibacterial natural compounds, J. Nat. Sci. Biol. Med, vol.4, pp.51-57, 2013.

D. J. Tipper and J. L. Strominger, Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-Dalanyl-D-alanine, Proc. Natl. Acad. Sci. U. S. A, vol.54, pp.1133-1174, 1965.

P. E. Tomatis, R. M. Rasia, L. Segovia, and A. J. Vila, Mimicking natural evolution in metallo-?-lactamases through second-shell ligand mutations, Proc. Natl. Acad. Sci. U. S. A, vol.102, pp.13761-13767, 2005.

D. Tondi, S. Calò, B. K. Shoichet, and M. P. Costi, Structural study of phenyl boronic acid derivatives as AmpC ?-lactamase inhibitors, Bioorg. Med. Chem. Lett, vol.20, pp.3416-3419, 2010.

L. S. Tzouvelekis, M. Gazouli, E. E. Prinarakis, E. Tzelepi, and N. J. Legakis, Comparative evaluation of the inhibitory activities of the novel penicillanic acid sulfone Ro 48-1220 against ?-lactamases that belong to groups 1, 2b, and 2be, Antimicrob. Agents Chemother, vol.41, pp.475-482, 1997.

C. Urban, E. Go, N. Mariano, B. J. Berger, A. I. Rubin et al., Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus, J. Infect. Dis, vol.167, pp.448-51, 1993.

C. Urban, J. J. Rahal, and B. Luft, Effect of a beta-lactamase inhibitor, tazobactam, on growth and penicillin-binding proteins of Borrelia burgdorferi, FEMS Microbiol. Lett, vol.66, pp.113-119, 1991.

J. Velasco, L. Adrio, J. , A. Moreno, M. Díez et al., Environmentally safe production of 7-aminodeacetoxycephalosporanic acid (7-ADCA) using recombinant strains of Acremonium chrysogenum, Nat. Biotechnol, vol.18, pp.857-61, 2000.

M. L. Verdonk, I. Giangreco, R. J. Hall, O. Korb, P. N. Mortenson et al., Docking Performance of Fragments and Druglike Compounds, J. Med. Chem, vol.54, pp.5422-5431, 2011.

C. Vidaillac, S. N. Leonard, H. S. Sader, R. N. Jones, and M. J. Rybak, In vitro activity of ceftaroline alone and in combination against clinical isolates of resistant gram-negative pathogens, including ?-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa, Antimicrob. Agents Chemother, vol.53, pp.2360-2366, 2009.

W. Vollmer, D. Blanot, D. Pedro, and M. A. , Peptidoglycan structure and architecture, FEMS Microbiol. Rev, vol.32, pp.149-167, 2008.

T. R. Walsh, M. A. Toleman, L. Poirel, and P. Nordmann, Metallo-?-lactamases: the quiet before the storm?, Clin. Microbiol. Rev, vol.18, pp.306-331, 2005.

Z. Wang, W. Fast, A. M. Valentine, and S. J. Benkovic, Metallo-?-lactamase: structure and mechanism, Curr. Opin. Chem. Biol, vol.3, pp.614-636, 1999.

D. White, J. Drummond, and C. Fuqua, The physiology and biochemistry of prokaryotes, vol.632, 2011.

J. D. Williams, ?-Lactamase inhibition and in vitro activity of sulbactam and sulbactam/cefoperazone, Clin. Infect. Dis, vol.24, pp.494-501, 1997.

M. L. Winkler, E. A. Rodkey, M. A. Taracila, S. M. Drawz, C. R. Bethel et al., Design and exploration of novel boronic acid inhibitors reveals important interactions with a clavulanic acid-resistant sulfhydryl-variable (SHV) ?-lactamase, J. Med. Chem, vol.56, pp.1084-97, 2013.

A. Wlodawer, W. Minor, Z. Dauter, and M. Jaskolski, Protein crystallography for non-crystallographers, or how to get the best (but not more) from published macromolecular structures, FEBS J, vol.275, pp.1-21, 2008.

D. Xu, D. Xie, and H. Guo, Catalytic Mechanism of Class B2 Metallo-?-lactamase, J. Biol. Chem, vol.281, pp.8740-8747, 2006.

M. Xu, A. Unzue, J. Dong, D. Spiliotopoulos, C. Nevado et al., Discovery of CREBBP Bromodomain Inhibitors by High-Throughput Docking and Hit Optimization Guided by Molecular Dynamics, J. Med. Chem, vol.59, pp.1340-1349, 2016.

Y. Yang, N. Bhachech, and K. Bush, Biochemical comparison of imipenem, meropenem and biapenem: permeability, binding to penicillin-binding proteins, and stability to hydrolysis by ?-lactamases, J. Antimicrob. Chemother, vol.35, pp.75-84, 1995.

A. Yoshizumi, Y. Ishii, D. M. Livermore, N. Woodford, S. Kimura et al., Efficacies of calcium-EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 ?-lactamase, J. Infect. Chemother, vol.19, pp.992-997, 2013.

A. Zapun, C. Contreras-martel, and T. Vernet, Penicillin-binding proteins and ?-lactam resistance, FEMS Microbiol. Rev, vol.32, pp.361-385, 2008.
URL : https://hal.archives-ouvertes.fr/hal-01158934

A. Zervosen, M. H. Valladares, B. Devreese, C. Prosperi-meys, H. Adolph et al., Inactivation of Aeromonas hydrophila metallo-?-lactamase by cephamycins and moxalactam, Eur. J. Biochem, vol.268, pp.3840-3850, 2001.

G. G. Zhanel, R. Wiebe, L. Dilay, K. Thomson, E. Rubinstein et al., Comparative Review of the Carbapenems. Drugs, vol.67, pp.1027-1052, 2007.

M. Zheng and D. Xu, New Delhi metallo-?-lactamase I: substrate binding and catalytic mechanism, J. Phys. Chem. B, vol.117, pp.11596-607, 2013.

G. A. Jacoby, AmpC Beta-Lactamases, Clin. Microbiol. Rev, vol.22, issue.1, pp.161-82, 2009.

L. Fang, J. Sun, L. Li, H. Deng, T. Huang et al., Dissemination of the Chromosomally Encoded CMY-2 Cephalosporinase Gene in Escherichia Coli Isolated from Animals, Int. J. Antimicrob. Agents, vol.46, issue.2, pp.209-213, 2015.

T. Naas, S. Oueslati, R. A. Bonnin, M. L. Dabos, A. Zavala et al., Spectrum Cephalosporinases in Escherichia Coli, Antimicrob. Agents Chemother, vol.50, issue.7, pp.2573-2576, 2006.

T. Kieser, Factors Affecting the Isolation of CCC DNA from Streptomyces Lividans and Escherichia Coli, Plasmid, vol.12, issue.1, pp.19-36, 1984.

G. Cao, M. W. Allard, M. Hoffmann, S. R. Monday, T. Muruvanda et al., Complete Sequences of Six IncA/C Plasmids of Multidrug-Resistant Salmonella Enterica Subsp, Enterica Serotype Newport. Genome Announc, vol.2015, issue.1, pp.27-42

S. D. Kotsakis, V. Miriagou, E. E. Vetouli, E. Bozavoutoglou, E. Lebessi et al., Increased Hydrolysis of Oximino-?-Lactams by CMY-107, a Tyr199Cys Mutant Form of CMY-2 Produced by Escherichia Coli, Antimicrob. Agents Chemother, vol.59, issue.12, pp.7894-7898, 2015.

A. Endimiani, Y. Doi, C. R. Bethel, M. Taracila, J. M. Adams-haduch et al., Enhancing Resistance to Cephalosporins in Class C Beta-Lactamases: Impact of Gly214Glu in CMY-2, Biochemistry, vol.2010, issue.5, pp.1014-1023

C. Bauvois, A. S. Ibuka, A. Celso, J. Alba, Y. Ishii et al., Kinetic Properties of Four Plasmid-Mediated AmpC Beta-Lactamases, Antimicrob. Agents Chemother, vol.49, issue.10, pp.4240-4246, 2005.

M. J. Skalweit, M. Li, B. C. Conklin, M. A. Taracila, R. A. Hutton et al., Substitutions in CMY-2 ?-Lactamase Increase Catalytic Efficiency for Cefoxitin and Inactivation Rates for Tazobactam, Antimicrob. Agents Chemother, vol.2013, issue.4, pp.1596-1602

S. Dahyot and H. Mammeri, Hydrolysis Spectrum Extension of CMY-2-like ?-Lactamases Resulting from Structural Alteration in the Y-X-N Loop, Antimicrob. Agents Chemother, vol.56, issue.3, pp.1151-1156, 2012.

M. Kusumoto, T. Ooka, Y. Nishiya, Y. Ogura, T. Saito et al., Insertion Sequence-Excision Enhancer Removes Transposable Elements from Bacterial Genomes and Induces Various Genomic Deletions, Nat. Commun, vol.2011, issue.1, p.152

S. T. Lefurgy, V. N. Malashkevich, J. T. Aguilan, E. Nieves, E. C. Mundorff et al., Analysis of the Structure and Function of FOX-4 Cephamycinase, Antimicrob. Agents Chemother, vol.60, issue.2, pp.717-728, 2016.

V. L. Thomas, A. C. Mcreynolds, and B. K. Shoichet, Structural Bases for Stability-Function Tradeoffs in Antibiotic Resistance, J. Mol. Biol, vol.396, issue.1, pp.47-59, 2010.

M. Berrazeg, K. Jeannot, V. Y. Ntsogo-enguéné, I. Broutin, S. Loeffert et al., Mutations in ?-Lactamase AmpC Increase Resistance of Pseudomonas Aeruginosa Isolates to Antipseudomonal Cephalosporins, Antimicrob. Agents Chemother, vol.59, issue.10, pp.6248-6255, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01693067

S. D. Kotsakis, V. Miriagou, E. E. Vetouli, E. Bozavoutoglou, E. Lebessi et al., Increased Hydrolysis of Oximino-?-Lactams by CMY-107, a Tyr199Cys Mutant Form of CMY-2 Produced by Escherichia Coli, Antimicrob. Agents Chemother, vol.59, issue.12, pp.7894-7898, 2015.

S. D. Kotsakis, L. S. Tzouvelekis, E. Petinaki, E. Tzelepi, and V. Miriagou, Effects of the Val211Gly Substitution on Molecular Dynamics of the CMY-2 Cephalosporinase: Implications on Hydrolysis of Expanded-Spectrum Cephalosporins, Proteins Struct. Funct. Bioinforma, vol.79, issue.11, pp.3180-3192, 2011.

L. Dortet, S. Oueslati, K. Jeannot, D. Tandé, T. Naas et al., Genetic and Biochemical Characterization of OXA-405, an OXA-48-Type Extended-Spectrum ?-Lactamase without Significant Carbapenemase Activity, Antimicrob. Agents Chemother, vol.59, issue.7, pp.3823-3828, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01689515

E. Zankari, H. Hasman, S. Cosentino, M. Vestergaard, S. Rasmussen et al., Identification of Acquired Antimicrobial Resistance Genes

, J. Antimicrob. Chemother, vol.2012, issue.11, pp.2640-2644

A. Carattoli, E. Zankari, A. García-fernández, M. Voldby-larsen, O. Lund et al., Silico Detection and Typing of Plasmids Using PlasmidFinder and Plasmid Multilocus Sequence Typing, vol.58, pp.3895-3903, 2014.

S. F. Altschul, W. Gish, W. Miller, E. W. Myers, and D. J. Lipman, Basic Local Alignment Search Tool, J. Mol. Biol, vol.215, issue.3, pp.403-410, 1990.

T. J. Carver, K. M. Rutherford, M. Berriman, M. Rajandream, B. G. Barrell et al., ACT: The Artemis Comparison Tool, Bioinformatics, vol.21, issue.16, pp.3422-3423, 2005.

M. M. Bradford, A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding, Anal. Biochem, vol.72, pp.248-254, 1976.

W. Kabsch, Integration, Scaling, Space-Group Assignment and Post-Refinement, Acta Crystallogr. D. Biol. Crystallogr, pp.133-144, 2010.

C. Vonrhein, C. Flensburg, P. Keller, A. Sharff, O. Smart et al., Data Processing and Analysis with the AutoPROC Toolbox, Acta Crystallogr

. Sect, . Biol, and . Crystallogr, , vol.67, pp.293-302, 2011.

P. R. Evans and G. N. Murshudov, How Good Are My Data and What Is the Resolution?, Acta Crystallogr. D. Biol. Crystallogr, pp.1204-1214, 2013.

M. D. Winn, C. C. Ballard, K. D. Cowtan, E. J. Dodson, P. Emsley et al., , p.4

, Suite and Current Developments, Acta Crystallogr. D. Biol. Crystallogr, vol.67, pp.235-242, 2011.

A. J. Mccoy, R. W. Grosse-kunstleve, P. D. Adams, M. D. Winn, L. C. Storoni et al., J. Phaser Crystallographic Software. J. Appl. Crystallogr, vol.40, issue.4, pp.658-674, 2007.

P. Emsley, B. Lohkamp, W. G. Scott, K. Cowtan, . Features et al.,

, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.66, issue.4, pp.486-501, 2010.

G. Bricogne, E. Blanc, M. Brandl, C. Flensburg, P. Keller et al., , 2017.

G. N. Murshudov, P. Skubák, A. A. Lebedev, N. S. Pannu, R. A. Steiner et al., REFMAC 5 for the Refinement of Macromolecular Crystal Structures, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.67, issue.4, pp.355-367, 2011.

V. B. Chen, W. B. Arendall, J. J. Headd, D. A. Keedy, R. M. Immormino et al., MolProbity : All-Atom Structure Validation for Macromolecular Crystallography, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.66, issue.1, pp.12-21, 2010.

L. Schrödinger, The PyMOL Molecular Graphics System, Version 1.8, 2015.

E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt et al., UCSF Chimera -A Visualization System for Exploratory Research and Analysis, J. Comput. Chem, issue.13, pp.1605-1612, 2004.

M. L. Verdonk, J. C. Cole, M. J. Hartshorn, C. W. Murray, and R. D. Taylor, Improved Protein-Ligand Docking Using GOLD, Proteins Struct. Funct. Bioinforma, vol.52, issue.4, pp.609-623, 2003.

S. Pronk, S. Páll, R. Schulz, P. Larsson, P. Bjelkmar et al., 5: A High-Throughput and Highly Parallel Open Source Molecular Simulation Toolkit, Bioinformatics, vol.2013, issue.7, pp.845-854

G. A. Kaminski, R. A. Friesner, J. Tirado-rives, W. L. Jorgensen, T. Naas et al., Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on, Peptides J. Phys. Chem. B, vol.99, issue.1, pp.865-79, 1999.

T. Naas, S. Oueslati, R. A. Bonnin, M. L. Dabos, A. Zavala et al., Beta-Lactamase DataBase (BLDB) -Structure and Function, J. Enz. Inh. Med. Chem, vol.32, pp.917-919, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02119817

. Carbapenemases, Curr. Drug. Targets, vol.17, issue.9, pp.1061-71

L. Poirel, A. Potron, and P. Nordmann, , 2012.

, OXA-48-like carbapenemases: the phantom menace, J. Antimicrob.Chemother, vol.67, pp.1597-1606

S. Oueslati, P. Nordmann, and L. Poirel, Heterogeneous hydrolytic features for OXA-48-like ?-lactamases, J. Antimicrob. Chemother, vol.70, issue.4, pp.1059-63, 2015.

S. Gomez, F. Pasteran, D. Faccone, M. Bettiol, O. Veliz et al., Intrapatient emergence of OXA-247: a novel carbapenemase found in a patient previously infected with OXA-163-producing Klebsiella pneumoniae, Clin. Microbiol, Infect, vol.19, issue.5, pp.233-238, 2013.

L. N. Philippon, T. Naas, A. T. Bouthors, V. Barakett, and P. Nordmann, OXA-18, a class D clavulanic acid-inhibited extended-spectrum beta-lactamase from Pseudomonas aeruginosa, Antimicrob. Agents Chemother, vol.41, issue.10, pp.2188-95, 1997.

J. D. Docquier, V. Calderone, F. De-luca, M. Benvenuti, F. Giuliani et al., Crystal structure of the OXA-48 ?-lactamase reveals mechanistic diversity among class D carbapenemases, Chem. Biol, vol.16, pp.540-547, 2009.

F. De-luca, M. Benvenuti, F. Carboni, C. Pozzi, G. M. Rossolini et al., Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D ?-lactamase OXA-10 by rational protein design, Proc. Natl. Acad. Sci. USA, vol.108, pp.18424-18453, 2011.

O. Almog, A. González, D. Klein, H. M. Greenblatt, S. Braun et al., , p.The, 2003.

. Å-crystal-structure-of-sphericase, A Calcium-Loaded Serine Protease from Bacillus Sphaericus, J. Mol. Biol, vol.332, issue.5, pp.1071-1082

D. Sychantha, D. J. Little, R. N. Chapman, G. Boons, H. Robinson et al., PatB1 Is an O-Acetyltransferase That Decorates Secondary Cell Wall Polysaccharides, Nat. Chem. Biol, 2017.

C. Keller, P. Paciorek, W. Roversi, P. Sharff, A. Smart et al., , 2011.

. Autobuster, Glob. Phasing Ltd, 2014.

G. N. Murshudov, P. Skubák, A. A. Lebedev, N. S. Pannu, R. A. Steiner et al., REFMAC 5 for the Refinement of Macromolecular Crystal Structures, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.67, issue.4, pp.355-367, 2011.

V. B. Chen, W. B. Arendall, J. J. Headd, D. A. Keedy, R. M. Immormino et al., MolProbity : All-Atom Structure Validation for Macromolecular Crystallography, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.66, issue.1, pp.12-21, 2010.

L. L. Schrödinger, The {PyMOL} Molecular Graphics System, Version~1, 2015.

E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt et al., UCSF Chimera -A Visualization System for Exploratory Research and Analysis, J. Comput. Chem, vol.25, issue.13, pp.1605-1612, 2004.

S. Pronk, S. Páll, R. Schulz, P. Larsson, P. Bjelkmar et al., GROMACS 4.5: A High-Throughput and Highly Parallel Open Source Molecular Simulation Toolkit, vol.29, pp.845-854, 2013.

G. A. Friesner, *. , R. A. , J. Jorgensen, and W. L. , Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides ?, 2001.

R. Ambler and R. P. , The structure of ?-lactamases, Philos. Trans. R. Soc. Lond. B. Biol. Sci, vol.289, pp.321-352, 1980.

M. Bhattacharya, M. Toth, N. T. Antunes, C. A. Smith, and S. B. Vakulenko, Structure of the extendedspectrum class C ?-lactamase ADC-1 from Acinetobacter baumannii, Acta Crystallogr. D. Biol. Crystallogr, vol.70, pp.760-71, 2014.

G. Bricogne, E. Blanc, M. Brandl, C. Flensburg, P. Keller et al.,

V. B. Chen, W. B. Arendall, J. J. Headd, D. A. Keedy, R. M. Immormino et al., MolProbity : all-atom structure validation for macromolecular crystallography, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.66, pp.12-21, 2010.

L. Dabos, P. Bogaerts, R. A. Bonnin, A. Zavala, P. Sacré et al., Genetic and Biochemical Characterization of OXA-519, a Novel OXA-48-Like ?-Lactamase, Antimicrob. Agents Chemother, vol.62, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02568064

L. Dabos, J. E. Raczynska, P. Bogaerts, A. Zavala, R. A. Bonnin et al., Structural plasticity of class D ?-lactamases: OXA-517, a novel OXA-48 variant with carbapenem and expanded spectrum cephalosporin hydrolysis, 2018.

L. Dabos, A. Zavala, R. A. Bonnin, O. Beckstein, P. Retailleau et al., Substrate specificity of OXA-48 modified by ?5-?6 loop replacement, 2018.

L. Dabos, A. Zavala, L. Dortet, R. A. Bonnin, O. Beckstein et al., Role of the loop ?5-?6 in the substrate specificity of OXA-48, 2018.

J. Docquier, V. Calderone, D. Luca, F. Benvenuti, M. Giuliani et al., Crystal Structure of the OXA-48 ?-Lactamase Reveals Mechanistic Diversity among Class D Carbapenemases, Chem. Biol, vol.16, pp.540-547, 2009.

L. Dortet, S. Oueslati, K. Jeannot, D. Tandé, T. Naas et al., Genetic and biochemical characterization of OXA-405, an OXA-48-type extended-spectrum ?-lactamase without significant carbapenemase activity, Antimicrob. Agents Chemother, vol.59, pp.3823-3831, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01689515

P. Emsley, B. Lohkamp, W. G. Scott, and K. Cowtan, Features and development of Coot, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.66, pp.486-501, 2010.

P. R. Evans and G. N. Murshudov, How good are my data and what is the resolution?, Acta Crystallogr. D. Biol. Crystallogr, vol.69, pp.1204-1218, 2013.

C. Héritier, L. Poirel, A. D. Nordmann, and P. , Genetic and functional analysis of the chromosome-encoded carbapenem-hydrolyzing oxacillinase OXA-40 of Acinetobacter baumannii, Antimicrob. Agents Chemother, vol.47, pp.268-73, 2003.

P. G. Higgins, L. Poirel, M. Lehmann, P. Nordmann, and H. Seifert, OXA-143, a Novel Carbapenem-Hydrolyzing Class D ?-Lactamase in Acinetobacter baumannii, Antimicrob. Agents Chemother, vol.53, pp.5035-5038, 2009.

W. Kabsch, Integration, scaling, space-group assignment and post-refinement, Acta Crystallogr. D. Biol. Crystallogr, vol.66, pp.133-177, 2010.

K. Kaitany, N. Klinger, C. M. June, M. E. Ramey, R. A. Bonomo et al., Structures of the class D Carbapenemases OXA-23 and OXA-146: mechanistic basis of activity against carbapenems, extended-spectrum cephalosporins, and aztreonam, Antimicrob. Agents Chemother, vol.57, pp.4848-55, 2013.

R. M. Keegan, M. D. Winn, and . Iucr, Automated search-model discovery and preparation for structure solution by molecular replacement, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.63, pp.447-457, 2007.

C. T. Lohans, D. Y. Wang, C. Jorgensen, S. T. Cahill, I. J. Clifton et al., 13C-Carbamylation as a mechanistic probe for the inhibition of class D ?-lactamases by avibactam and halide ions, Org. Biomol. Chem, vol.15, pp.6024-6032, 2017.

F. De-luca, M. Benvenuti, F. Carboni, C. Pozzi, G. M. Rossolini et al., Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D ?-lactamase OXA-10 by rational protein design, Proc. Natl. Acad. Sci. U. S. A, vol.108, pp.18424-18433, 2011.

J. M. Mitchell, J. R. Clasman, C. M. June, K. Kaitany, J. R. Lafleur et al., Structural Basis of Activity against Aztreonam and Extended Spectrum Cephalosporins for Two Carbapenem-Hydrolyzing Class D ?-Lactamases from Acinetobacter baumannii, Biochemistry, vol.54, pp.1976-1987, 2015.

G. N. Murshudov, P. Skubák, A. A. Lebedev, N. S. Pannu, R. A. Steiner et al., REFMAC 5 for the refinement of macromolecular crystal structures, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.67, pp.355-367, 2011.

T. Naas and P. Nordmann, OXA-type ?-lactamases, Curr. Pharm. Des, vol.5, pp.865-79, 1999.

T. Naas, S. Oueslati, R. A. Bonnin, M. L. Dabos, A. Zavala et al., Betalactamase database (BLDB) -structure and function, J. Enzyme Inhib. Med. Chem, vol.32, pp.917-919, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02119817

T. Naas, W. Sougakoff, A. Casetta, and P. Nordmann, Molecular characterization of OXA-20, a novel class D ?-lactamase, and its integron from Pseudomonas aeruginosa, Antimicrob. Agents Chemother, vol.42, pp.2074-83, 1998.

J. O'neill, Antimicrobial resistance: tackling a crisis for the health and wealth of nations, Rev. Antimicrob. Resist, vol.20, pp.1-16, 2014.

S. Oueslati, M. L. Dabos, A. Zavala, B. I. Iorga, and T. Naas, A greater than expected variability among OXA-48-like carbapenemases, Rom. Arch. Microbiol. Immunol, vol.77, pp.117-122, 2018.

M. P. Patel, L. Hu, V. Stojanoski, B. Sankaran, B. Prasad et al., The Drug-Resistant Variant P167S Expands the Substrate Profile of CTX-M ?-Lactamases for Oxyimino-Cephalosporin Antibiotics by Enlarging the Active Site upon Acylation, Biochemistry, vol.56, pp.3443-3453, 2017.

L. Poirel, M. Castanheira, A. Carrër, C. P. Rodriguez, R. N. Jones et al., OXA-163, an OXA-48-Related Class D ?-Lactamase with Extended Activity Toward Expanded-Spectrum Cephalosporins, Antimicrob. Agents Chemother, vol.55, pp.2546-2551, 2011.

L. Poirel, C. Héritier, V. Tolün, and P. Nordmann, Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae, Antimicrob. Agents Chemother, vol.48, pp.15-22, 2004.

L. Poirel, T. Naas, and P. Nordmann, Diversity, epidemiology, and genetics of class D ?lactamases, Antimicrob. Agents Chemother, vol.54, pp.24-38, 2010.

L. Poirel and P. Nordmann, Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology, Clin. Microbiol. Infect, vol.12, pp.826-836, 2006.

L. Poirel, A. Potron, and P. Nordmann, OXA-48-like carbapenemases: the phantom menace, J. Antimicrob. Chemother, vol.67, pp.1597-1606, 2012.

A. Potron, P. Nordmann, E. Lafeuille, A. Maskari, Z. et al., Characterization of OXA-181, a Carbapenem-Hydrolyzing Class D ?-Lactamase from Klebsiella pneumoniae, Antimicrob. Agents Chemother, vol.55, pp.4896-4899, 2011.

A. Potron, E. Rondinaud, L. Poirel, O. Belmonte, S. Boyer et al., Genetic and biochemical characterisation of OXA-232, a carbapenem-hydrolysing class D ?lactamase from Enterobacteriaceae, Int. J. Antimicrob. Agents, vol.41, pp.325-334, 2013.

L. Schrödinger, The PyMOL Molecular Graphics System, 2008.

V. Stojanoski, D. Chow, B. Fryszczyn, L. Hu, P. Nordmann et al., Structural Basis for Different Substrate Profiles of Two Closely Related Class D ?-Lactamases and Their Inhibition by Halogens, Biochemistry, vol.54, pp.3370-80, 2015.

L. Vercheval, C. Bauvois, A. Di-paolo, F. Borel, J. Ferrer et al., Three factors that modulate the activity of class D ?-lactamases and interfere with the post-translational carboxylation of Lys70, Biochem. J, vol.432, pp.495-504, 2010.

M. D. Winn, C. C. Ballard, K. D. Cowtan, E. J. Dodson, P. Emsley et al., Overview of the CCP4 suite and current developments, Acta Crystallogr. D. Biol. Crystallogr, vol.67, pp.235-277, 2011.

O. Beckstein, N. Michaud-agrawal, and T. B. Woolf, Quantitative Analysis of Water Dynamics in and near Proteins, Biophys. J, vol.96, p.601, 2009.

P. Bogaerts, T. Naas, V. Saegeman, R. A. Bonnin, A. Schuermans et al., OXA-427, a new plasmidborne carbapenem-hydrolysing class D ?-lactamase in Enterobacteriaceae, J. Antimicrob. Chemother, vol.72, pp.2469-2477, 2017.

M. M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem, vol.72, pp.248-54, 1976.

G. Bricogne, E. Blanc, M. Brandl, C. Flensburg, P. Keller et al.,

V. B. Chen, W. B. Arendall, J. J. Headd, D. A. Keedy, R. M. Immormino et al., MolProbity : all-atom structure validation for macromolecular crystallography, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.66, pp.12-21, 2010.

L. Dabos, A. Zavala, R. A. Bonnin, O. Beckstein, P. Retailleau et al., Substrate specificity of OXA-48 modified by ?5-?6 loop replacement, 2018.

J. Docquier, V. Calderone, D. Luca, F. Benvenuti, M. Giuliani et al., Crystal Structure of the OXA-48 ?-Lactamase Reveals Mechanistic Diversity among Class D Carbapenemases, Chem. Biol, vol.16, pp.540-547, 2009.

J. Docquier and S. Mangani, Structure-Function Relationships of Class D Carbapenemases, Curr. Drug Targets, vol.17, pp.1061-1071, 2016.

P. Emsley, B. Lohkamp, W. G. Scott, and K. Cowtan, Features and development of Coot, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.66, pp.486-501, 2010.

B. A. Evans and S. Amyes, OXA ?-lactamases, Clin. Microbiol. Rev, vol.27, pp.241-63, 2014.

P. R. Evans and G. N. Murshudov, How good are my data and what is the resolution?, Acta Crystallogr. D. Biol. Crystallogr, vol.69, pp.1204-1218, 2013.

D. Hagemans, I. Van-belzen, M. Luengo, T. Rüdiger, and S. , A script to highlight hydrophobicity and charge on protein surfaces. Front, Mol. Biosci, vol.2, p.56, 2015.

G. A. Kaminski, R. A. Friesner, J. Tirado-rives, and W. L. Jorgensen, Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides ?, 2001.

R. M. Keegan, M. D. Winn, and . Iucr, Automated search-model discovery and preparation for structure solution by molecular replacement, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.63, pp.447-457, 2007.

J. M. Mitchell, J. R. Clasman, C. M. June, K. Kaitany, J. R. Lafleur et al., Structural Basis of Activity against Aztreonam and Extended Spectrum Cephalosporins for Two Carbapenem-Hydrolyzing Class D ?-Lactamases from Acinetobacter baumannii, Biochemistry, vol.54, pp.1976-1987, 2015.

G. N. Murshudov, P. Skubák, A. A. Lebedev, N. S. Pannu, R. A. Steiner et al., REFMAC 5 for the refinement of macromolecular crystal structures, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.67, pp.355-367, 2011.

E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt et al., UCSF Chimera -A visualization system for exploratory research and analysis, J. Comput. Chem, vol.25, pp.1605-1612, 2004.

L. Poirel, T. Naas, and P. Nordmann, Diversity, epidemiology, and genetics of class D ?-lactamases, Antimicrob. Agents Chemother, vol.54, pp.24-38, 2010.

S. Pronk, S. Páll, R. Schulz, P. Larsson, P. Bjelkmar et al., 5: a high-throughput and highly parallel open source molecular simulation toolkit, Bioinformatics, vol.29, pp.845-854

L. Schrödinger, N. T. Antunes, N. K. Stewart, M. Toth, M. Kumarasiri et al., Structural basis for carbapenemase activity of the OXA-23 ?-lactamase from Acinetobacter baumannii, Chem. Biol, vol.20, pp.1107-1122, 2013.

, Breakpoint tables for interpretation of MICs and zone diameters, The European Committee on Antimicrobial Susceptibility, 2018.

C. Vonrhein, C. Flensburg, P. Keller, A. Sharff, O. Smart et al., Data processing and analysis with the autoPROC toolbox, Acta Crystallogr. Sect. D Biol. Crystallogr, vol.67, pp.293-302, 2011.

F. ?-de-luca, M. Benvenuti, F. Carboni, C. Pozzi, G. M. Rossolini et al., Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D ?-lactamase OXA-10 by rational protein design, Proc Natl Acad Sci, vol.108, pp.18424-18429, 2011.

W. L. Delano, The PyMOL Molecular Graphics System, 2014.

J. D. Docquier, V. Calderone, D. Luca, F. Benvenuti, M. Giuliani et al., Crystal structure of the OXA-48 ?-lactamase reveals mechanistic diversity among class D carbapenemases, Chem Biol, vol.16, pp.540-547, 2009.

L. Dortet, S. Oueslati, K. Jeannot, D. Tandé, T. Naas et al., Genetic and biochemical characterization of OXA-405, an OXA-48-Type Extended-Spectrum ?-Lactamase without Significant Carbapenemase Activity, Antimicrob Agents Chemother, vol.59, pp.3823-3828, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01689515

P. Emsley, B. Lohkamp, W. G. Scott, and K. Cowtan, Features and development of Coot, Acta Crystallogr D Biol Crystallogr, vol.66, pp.486-501, 2010.

C. Ewers, I. Stamm, Y. Pfeifer, L. H. Wieler, P. A. Kopp et al., Clonal spread of highly successful ST15-CTX-M-15 Klebsiella pneumoniae in companion animals and horses, J Antimicrob Chemother, vol.69, issue.10, pp.2676-80, 2014.

K. L. ?-fillgrove, S. Pakhomova, M. E. Newcomer, and R. N. Armstrong, Mechanistic diversity of fosfomycin resistance in pathogenic microorganisms, J Am Chem Soc, vol.125, issue.51, pp.15730-15731, 2003.

G. S. French, K. Wilson, L. Gauthier, R. A. Bonnin, L. Dortet et al., Retrospective and prospective evaluation of the Carbapenem inactivation method for the detection of carbapenemase-producing Enterobacteriaceae, Acta. Cryst, vol.34, issue.2, 1978.

D. Golemi, L. Maveyraud, S. Vakulenko, J. P. Samama, and S. Mobashery, Critical involvement of, 2001.

, class D ?-lactamases, Proc. Natl. Acad. Sci

S. , , vol.98, pp.14280-14285

T. D. Huang, L. Poirel, P. Bogaerts, C. Berhin, P. Nordmann et al., Temocillin and piperacillin/tazobactam resistance by disc diffusion as antimicrobial surrogate markers for the detection of carbapenemase-producing Enterobacteriaceae in geographical areas with a high prevalence of OXA-48 producers, J Antimicrob Chemother, vol.69, issue.2, pp.445-50, 2014.

C. M. June, T. J. Muckenthaler, E. C. Schroder, Z. L. Klamer, Z. Wawrzak et al., The structure of a doripenem-bound OXA-51 class D ?-lactamase variant with enhanced carbapenemase activity, Protein Sci, vol.25, issue.12, pp.2152-2163, 2016.

W. Kabsch, XDS. Acta Crystallogr D Biol Crystallogr, vol.66, issue.2, pp.125-157, 2010.

T. Kieser, Factors affecting the isolation of CCC DNA from Streptomyces lividans and Escherichia coli, Plasmid, vol.12, pp.19-36, 1984.

G. J. Kleywegt, M. R. Harris, J. Y. Zou, T. C. Taylor, A. Wählby et al., The Uppsala Electron-Density Server, Acta Crystallogr D Biol Crystallogr, vol.60, pp.2240-2249, 2004.

M. Kowiel, M. Jaskolski, and Z. Dauter, ACHESYM: an algorithm and server for standardized placement of macromolecular models in the unit cell, Acta Crystallogr D Biol Crystallogr, vol.70, pp.3290-3298, 2014.

M. Krug, M. S. Weiss, U. Heinemann, and U. Mueller, XDSAPP: a graphical user interface for the convenient processing of diffraction data using XDS, J. Appl. Cryst, vol.45, pp.568-572, 2012.

M. V. Larsen, S. Cosentino, S. Rasmussen, C. Friis, H. Hasman et al., Multilocus sequence typing of totalgenome-sequenced bacteria, J Clin Microbiol, vol.50, issue.4, pp.1355-61, 2012.

D. A. Leonard, R. A. Bonomo, and R. A. Powers, Class D ?-lactamases: A reappraisal after five decades, Acc. Chem. Res, vol.46, pp.2407-2415, 2013.

J. Li, J. B. Cross, T. Vreven, S. O. Meroueh, S. Mobashery et al., Lysine carboxylation in proteins: OXA-10 ?-lactamase, Proteins, vol.61, pp.246-257, 2005.

A. J. Mccoy, R. W. Grosse-kunstleve, P. D. Adams, M. D. Winn, L. C. Storoni et al., Phaser crystallographic software, J Appl Crystallogr, vol.40, pp.658-674, 2007.

D. ?-meziane-cherif, R. Bonnet, A. Haouz, and P. Courvalin, Structural insights into the loss of penicillinase and the gain of ceftazidimase activities by OXA-145 ?lactamase in Pseudomonas aeruginosa, J Antimicrob Chemother, vol.71, issue.2, pp.395-402, 2016.

J. M. Mitchell, J. R. Clasman, C. M. June, K. C. Kaitany, J. R. Lafleur et al., Structural basis of activity against aztreonam and extended spectrum cephalosporins for two carbapenemhydrolyzing class D ?-lactamases from Acinetobacter baumannii, Biochemistry, vol.54, issue.10, pp.1976-87, 2015.

G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew et al., AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, J Comput Chem, vol.30, pp.2785-2791, 2009.

M. M. ?-muntean, A. A. Muntean, L. Gauthier, E. Creton, G. Cotellon et al., Evaluation of the rapid carbapenem inactivation method (rCIM): a phenotypic screening test for carbapenemase-producing Enterobacteriaceae, J Antimicrob Chemother, vol.73, issue.4, pp.900-908, 2018.

G. N. Murshudov, P. Skubák, A. A. Lebedev, N. S. Pannu, R. A. Steiner et al., REFMAC5 for the refinement of macromolecular crystal structures, Acta Cryst, vol.67, pp.355-367, 2011.

T. Naas, W. Sougakoff, A. Casetta, and P. Nordmann, Molecular characterization of OXA-20, a novel class D ?-lactamase, and its integron from Pseudomonas aeruginosa, Antimicrob Agents Chemother, vol.42, pp.2074-83, 1998.

T. Naas, S. Oueslati, R. A. Bonnin, M. L. Dabos, A. Zavala et al., Beta-Lactamase DataBase (BLDB) -Structure and Function, J. Enz Inh Med Chem, vol.32, pp.917-919, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02119817

P. ?-normann, L. Poirel, and L. Dortet, Rapid detection of carbapenemase-producing Enterobacteriacea, Emerg Infect Dis, vol.18, p.1503, 2012.

S. Oueslati, P. Nordmann, and L. Poirel, Heterogeneous hydrolytic features for OXA-48-like ?-lactamases, J. Antimicrob.Chemother, vol.70, pp.1059-63, 2015.

M. Paetzel, F. Danel, L. De-castro, S. C. Mosimann, M. G. Page et al., , 2000.

, OXA-517, an OXA-48-like ?-lactamase with ESBL and carbapenemase activity 21 Structure of the Class D Beta-Lactamase OXA

, Nat. Struct. Biol, vol.7, issue.10, pp.918-925

L. Pernot, F. Frénois, T. Rybkine, L. 'hermite, G. Petrella et al., Crystal structures of the class D beta-lactamase OXA-13 in the native form and in complex with meropenem, J Mol Biol, vol.310, issue.4, pp.859-74, 2001.

L. Poirel, C. Heritier, V. Tolun, and P. Nordmann, Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae, Antimicrob Agents Chemother, vol.48, pp.15-22, 2004.

L. Poirel, T. Naas, and P. Nordmann, Diversity, epidemiology, and genetics of class D blactamases, Antimicrob Agents Chemother, vol.54, pp.24-38, 2010.

L. Poirel, M. Castanheira, A. Carrer, C. P. Rodriguez, R. N. Jones et al., OXA-163, an OXA-48-related class D ?lactamase with extended activity toward expanded-spectrum cephalosporins, 2011.

, Antimicrob Agents Chemother, vol.55, pp.2546-2551

L. Poirel, A. Potron, and P. Nordmann, OXA-48-like carbapenemases: the phantom menace, J Antimicrob Chemother, vol.67, pp.1597-1606, 2012.

L. Poirel, R. A. Bonnin, and P. Nordmann, Genetic features of the widespread plasmid coding for the carbapenemase OXA-48, 2012.

, Antimicrob. Agents Chemother, vol.56, pp.559-562

A. Potron, P. Nordmann, E. Lafeuille, A. Maskari, Z. et al., Characterization of OXA-181, a carbapenem-hydrolyzing class D ?-lactamase from Klebsiella pneumoniae, Antimicrob Agents Chemother, vol.55, pp.4896-4899, 2011.

A. ?-potron, E. Rondinaud, L. Poirel, O. Belmonte, S. Boyer et al., Genetic and biochemical characterisation of OXA-232, a carbapenem-hydrolysing class D ?lactamase from Enterobacteriaceae, Int J Antimicrob Agents, vol.41, pp.325-329, 2013.

A. ?-potron, L. Poirel, and P. Nordmann, Derepressed transfer properties leading to the efficient spread of the plasmid encoding carbapenemase OXA-48, Antimicrob Agents Chemother, vol.58, pp.467-71, 2014.

M. S. Ramirez and M. E. Tolmasky, Clin Microbiol Rev, vol.20, pp.440-58, 2010.

, Aminoglycoside Modifying Enzymes. Drug Resist Updat, vol.13, issue.6, pp.151-171

R. J. Read, P. D. Adams, and A. J. Mccoy, Intensity statistics in the presence of translational noncrystallographic symmetry, Acta Crystallogr D Biol Crystallogr, vol.69, issue.2, pp.176-83, 2013.

C. Rodrigues, J. Bavlovi?, E. Machado, E. Machado, J. Amorim et al., KPC-3-Producing Klebsiella pneumoniae in Portugal Linked to Previously Circulating Non-CG258 Lineages and Uncommon Genetic Platforms (Tn4401d-IncFIA and Tn4401d-IncN), Front Microbiol, vol.7, p.1000, 2016.

?. Rodríguez-martínez, J. M. , D. De-alba, P. Briales, A. Machuca et al., Contribution of OqxAB efflux pumps to quinolone resistance in extended-spectrum?-lactamase-producing Klebsiella pneumoniae, J Antimicrob Chemother, vol.68, issue.1, pp.68-73, 2013.

K. D. Schneider, C. J. Ortega, N. A. Renck, R. A. Bonomo, R. A. Powers et al., Structures of the class D carbapenemase OXA-24 from Acinetobacter baumannii in complex with doripenem, Mol Biol, vol.406, issue.4, pp.583-94, 2011.

O. Skold, Sulfonamide resistance: mechanisms and trends, Drug Resist. Updates, vol.3, pp.155-160, 2000.

O. S. Smart, T. O. Womack, A. Sharff, C. Flensburg, P. Keller et al., Structural basis for carbapenemase activity of the OXA-23 ?lactamase from Acinetobacter baumannii, Chem Biol, vol.20, issue.9, pp.1107-1122, 2011.

V. Stojanoski, D. C. Chow, B. Fryszczyn, L. Hu, P. Nordmann et al., , 2015.

G. W. Sundin, Distinct recent lineages of the strA-strB streptomycin-resistance genes in clinical and environmental bacteria, Curr Microbiol, vol.45, issue.1, pp.63-72, 2002.

L. F. ?-ten-eyck, Crystallographic fast Fourier transforms, Acta Cryst, vol.29, pp.183-191, 1973.

M. Toth, N. T. Antunes, N. K. Stewart, H. Frase, M. Bhattacharya et al., Class D ?-lactamases do exist in Grampositive bacteria, Nat Chem Biol, vol.203, issue.1, pp.9-14, 2015.

O. Trott and A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J Comput Chem, vol.31, issue.2, pp.455-61, 2010.

M. D. Winn, C. C. Ballard, K. D. Cowtan, E. J. Dodson, P. Emsley et al., Overview of the CCP4 suite and current developments, Acta Crystallogr D Biol Crystallogr, vol.67, pp.235-277, 2011.

E. Zankari, H. Hasman, S. Cosentino, M. Vestergaard, S. Rasmussen et al., Identification of acquired antimicrobial resistance genes, J. Antimicrob. Chemother, vol.67, issue.11, pp.2640-2644, 2012.

K. Zhou, M. Lokate, R. H. Deurenberg, M. Tepper, J. P. Arends et al., Use of whole-genome sequencing to trace, control and characterize the regional expansion of extended-spectrum ?-lactamase producing ST15 Klebsiella pneumoniae, Sci Rep, vol.6, p.20840, 2016.

R. P. Ambler, The structure of ?-lactamases, Philos Trans R Soc London B Biol Sci, vol.289, pp.321-331, 1980.

J. Lamotte-brasseur, J. Knox, A. Kelly, P. Charlier, E. Fonzé et al., The structures and catalytic mechanisms of active-site serine ?-lactamases, Biotechnol Genet Eng. Rev, vol.12, pp.189-230, 1994.

T. Naas and P. Nordmann, OXA-type ?-lactamases, Curr Pharm Des, vol.5, pp.865-879, 1999.

L. Poirel, C. Heritier, V. Tolun, and P. Nordmann, Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae, Antimicrob Agents Chemother, vol.48, pp.15-22, 2004.

D. Aubert, T. Naas, C. Héritier, L. Poirel, and P. Nordmann, Functional characterization of IS1999, an IS4 family element involved in mobilization and expression of beta-lactam resistance genes, J Bacteriol, vol.188, pp.6506-6514, 2006.

J. D. Docquier, V. Calderone, D. Luca, F. Benvenuti, M. Giuliani et al., Crystal structure of the OXA-48 ?-lactamase reveals mechanistic diversity among class D carbapenemases, Chem Biol, vol.16, pp.540-547, 2009.

T. Naas, S. Oueslati, R. A. Bonnin, M. L. Dabos, A. Zavala et al., Beta-Lactamase DataBase (BLDB) -structure and function, J Enz Inh Med Chem, vol.32, pp.917-919, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02119817

C. A. Smith, N. T. Antunes, N. K. Stewart, H. Frase, M. Toth et al., Structural basis for enhancement of carbapenemase activity in the OXA-51 family of class D ?-lactamases, ACS Chem Biol, vol.10, pp.1791-1796, 2015.

P. Nordmann, L. Poirel, and L. Dortet, Rapid detection of carbapenemaseproducing Enterobacteriacea, Emerg Infect Dis, vol.18, pp.1503-1507, 2012.

S. Bernabeu, L. Dortet, and T. Naas, Evaluation of the ?-CARBA? test, a colorimetric test for the rapid detection of carbapenemase activity in Gram-negative bacilli, J Antimicrob Chemother, vol.72, pp.1646-1658, 2017.

P. Bogaerts, S. Yunus, M. Massart, T. D. Huang, and Y. Glupczynski, Evaluation of the BYG carba test, a new electrochemical assay for rapid laboratory detection of carbapenemase-producing Enterobacteriaceae, J Clin Microbiol, vol.54, pp.349-358, 2016.

P. Bogaerts, S. Oueslati, D. Meunier, C. Nonhoff, S. Yunus et al., Multicentre evaluation of the BYG Carba v2.0 test, a simplified electrochemical assay for the rapid laboratory detection of carbapenemase-producing Enterobacteriaceae, Sci Rep, vol.7, issue.1, p.9937, 2017.

H. Boutal, A. Vogel, S. Bernabeu, K. Devilliers, E. Creton et al., A multiplex lateral flow immunoassay for the rapid identification of NDM-, KPC-, IMP-and VIM-type and OXA-48-like carbapenemaseproducing Enterobacteriaceae, J Antimicrob Chemother, vol.73, pp.909-915, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02629307

L. Dortet, A. Jousset, V. Sainte-rose, G. Cuzon, and T. Naas, Prospective evaluation of the OXA-48 K-SeT assay, an immunochromatographic test for the rapid detection of OXA-48-type carbapenemases, J Antimicrob Chemother, vol.71, pp.1834-1840, 2016.

S. Oueslati, P. Nordmann, and L. Poirel, Heterogeneous hydrolytic features for OXA-48-like ?-lactamase, J Antimicrob Chemother, vol.70, pp.1059-1063, 2015.

P. Poirel, T. Naas, and P. Nordmann, Diversity, epidemiology, and genetics of class D ?-lactamases, Antimicrob Agents Chemother, vol.54, pp.24-38, 2010.

F. Couture, J. Lachapelle, and R. C. Levesque, Phylogeny of LCR-1 and OXA-5 with class A and class D ?-lactamases, Mol Microbiol, vol.6, pp.1693-1705, 1992.

F. De-luca, M. Benvenuti, F. Carboni, C. Pozzi, G. M. Rossolini et al., Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D ?-lactamase OXA-10 by rational protein OXA-519, a Weak Imipenem-Hydrolyzing OXA-48 Variant Antimicrobial Agents and Chemotherapy, 2011.

, Proc Natl Acad Sci U S A, vol.108, pp.18424-18429

V. Stojanoski, D. C. Chow, B. Fryszczyn, L. Hu, P. Nordmann et al., Structural basis for different substrate profiles of two closely related class D ?-lactamases and their inhibition by halogens, Biochemistry, vol.54, pp.3370-3380, 2015.

J. M. Mitchell and D. A. Leonard, Common clinical substitutions enhance the carbapenemase activity of OXA-51-like class D ?-lactamases from Acinetobacter spp, Antimicrob Agents Chemother, vol.58, pp.7015-7016, 2014.

C. M. June, T. J. Muckenthaler, E. C. Schroder, Z. L. Klamer, Z. Wawrzak et al., The structure of a doripenem-bound OXA-51 class D ?-lactamase variant with enhanced carbapenemase activity, Protein Sci, vol.25, pp.2152-2163, 2016.

A. B. Jousset, L. Dabos, R. A. Bonnin, D. Girlich, A. Potron et al., CTX-M-15-producing Shewanella species clinical isolate expressing OXA-535, a chromosome-encoded OXA-48 variant, putative progenitor of the plasmid-encoded OXA-436, Antimicrob Agents Chemother, vol.62, pp.1879-1896, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01690618

M. Larsen, S. Cosentino, S. Rasmussen, C. Friis, H. Hasman et al., Multilocus sequence typing of total-genome-sequenced bacteria, J Clin Microbiol, vol.50, pp.1355-1361, 2012.

C. Rodrigues, J. Bavlovi?, E. Machado, E. Machado, J. Amorim et al., KPC-3-producing Klebsiella pneumoniae in Portugal linked to previously circulating non-CG258 lineages and uncommon genetic platforms (Tn4401d-IncFIA and Tn4401d-IncN), 2016.

K. Zhou, M. Lokate, R. H. Deurenberg, M. Tepper, J. P. Arends et al., Use of whole-genome sequencing to trace, control and characterize the regional expansion of extended-spectrum ?-lactamase producing ST15 Klebsiella pneumoniae, Sci Rep, vol.6, 2016.

C. Ewers, I. Stamm, Y. Pfeifer, L. H. Wieler, P. A. Kopp et al., Clonal spread of highly successful ST15-CTX-M-15 Klebsiella pneumoniae in companion animals and horses, J Antimicrob Chemother, vol.69, pp.2676-2680, 2014.

E. Zankari, H. Hasman, S. Cosentino, M. Vestergaard, S. Rasmussen et al., Identification of acquired antimicrobial resistance genes, J Antimicrob Chemother, vol.67, pp.2640-2644, 2012.

S. Raherison, T. Jove, M. Gaschet, E. Pinault, A. Tabesse et al., Expression of the aac(6=)-Ib-cr gene in class 1 integrons, Antimicrob Agents Chemother, vol.61, pp.2704-2720, 2017.

L. Poirel, R. A. Bonnin, and P. Nordmann, Genetic support and diversity of acquired extended-spectrum ?-lactamases in Gram-negative rods, Infect Genet Evol, vol.12, pp.883-893, 2012.

A. Fabrega, S. Madurga, E. Giralt, and J. Vila, Mechanism of action of and resistance to quinolones, Microb Biotechnol, vol.2, pp.40-61, 2009.

A. Potron, P. Nordmann, E. Lafeuille, A. Maskari, Z. et al., Characterization of OXA-181, a carbapenem-hydrolyzing class D ?-lactamase from Klebsiella pneumoniae, Antimicrob Agents Chemother, vol.55, pp.4896-4899, 2011.

A. Potron, E. Rondinaud, L. Poirel, O. Belmonte, S. Boyer et al., Genetic and biochemical characterisation of OXA-232, a carbapenem-hydrolysing class D ?-lactamase from Enterobacteriaceae, Int J Antimicrob Agents, vol.41, pp.325-329, 2013.

L. Poirel, R. A. Bonnin, and P. Nordmann, Genetic features of the widespread plasmid coding for the carbapenemase OXA-48, Antimicrob Agents Chemother, vol.56, pp.559-562, 2012.

A. Potron, L. Poirel, and P. Nordmann, Derepressed transfer properties leading to the efficient spread of the plasmid encoding carbapenemase OXA-48, Antimicrob Agents Chemother, vol.58, pp.467-471, 2014.

. Dabos, Antimicrobial Agents and Chemotherapy

P. Poirel, T. Naas, and . Nordmann, Diversity, epidemiology, and genetics of class D ?-lactamases, Antimicrob Agents Chemother, vol.54, pp.24-38, 2010.

D. Van-duin and Y. Doi, The global epidemiology of carbapenemaseproducing Enterobacteriaceae, Virulence, vol.8, pp.460-469, 2017.

L. Poirel, C. Heritier, V. Tolun, and P. Nordmann, Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae, Antimicrob Agents Chemother, vol.48, pp.15-22, 2004.

T. Naas, S. Oueslati, R. A. Bonnin, M. L. Dabos, A. Zavala et al., Beta-lactamase database (BLDB)-structure and function, J Enzyme Inhib Med Chem, vol.32, pp.917-919, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02119817

Ø. Samuelsen, F. Hansen, B. Aasnaes, H. Hasman, B. A. Lund et al., Dissemination and characteristics of a novel plasmid-encoded carbapenem-hydrolyzing class D ?-lactamase, OXA-436, found in isolates from four patients at six different hospitals in Denmark, Antimicrob Agents Chemother, vol.62, pp.1260-1277, 2018.

S. Oueslati, P. Nordmann, and L. Poirel, Heterogeneous hydrolytic features for OXA-48-like ?-lactamases, J Antimicrob Chemother, vol.70, pp.1059-1063, 2015.

D. Aubert, T. Naas, C. Heritier, L. Poirel, and P. Nordmann, Functional characterization of IS1999, an IS4 family element involved in mobilization and expression of ?-lactam resistance genes, J Bacteriol, vol.188, pp.6506-6514, 2006.

L. Poirel, R. A. Bonnin, and P. Nordmann, Genetic features of the widespread plasmid coding for the carbapenemase OXA-48, Antimicrob Agents Chemother, vol.56, pp.559-562, 2012.

H. E. Sidjabat, K. Kennedy, A. Silvey, P. Collignon, and D. Paterson, Emergence of blaOXA-181-carrying ColE plasmid in Klebsiella pneumoniae in Australia, Int J Antimicrob Agents, vol.41, pp.294-296, 2013.

L. Poirel, M. Castanheira, A. Carrer, C. P. Rodriguez, R. N. Jones et al., OXA-163, an OXA-48-related class D ?-lactamase with extended activity toward expanded-spectrum cephalosporins, Antimicrob Agents Chemother, vol.55, pp.22-33, 2011.

L. Poirel, C. Heritier, and P. Nordmann, Chromosome-encoded ambler class D ?-lactamase of Shewanella oneidensis as a progenitor of carbapenem-hydrolyzing oxacillinase, Antimicrob Agents Chemother, vol.48, pp.348-351, 2004.

M. Tacão, S. Araújo, M. Vendas, A. Alves, and I. Henriques, Shewanella species as the origin of blaOXA-48 genes: insights into gene diversity, associated phenotypes and possible transfer mechanisms, Int J Antimicrob Agents, vol.51, pp.340-348, 2018.

Z. Zong, Discovery of blaOXA-199 a chromosome-based blaOXA-48-like variant in Shewanella xiamenensis, PLoS One, vol.7, 2012.

A. Antonelli, D. Palo, D. M. Galano, A. Becciani, S. Montagnani et al., Intestinal carriage of Shewanella xiamenensis simulating carriage of OXA-48-producing Enterobacteriaceae, Diagn Microbiol Infect Dis, vol.82, pp.1-3, 2015.

A. Potron, L. Poirel, and P. Nordmann, Origin of OXA-181, an emerging carbapenem-hydrolyzing oxacillinase, as a chromosomal gene in Shewanella xiamenensis, Antimicrob Agents Chemother, vol.55, pp.4405-4407, 2011.

M. Tacão, A. Correia, and I. Henriques, Environmental Shewanella xiamenensis strains that carry bla OXA-48 or bla OXA-204 genes: additional proof for bla OXA-48-like gene origin, Antimicrob Agents Chemother, vol.57, pp.6399-6400, 2013.

D. M. Kim, C. I. Kang, C. S. Lee, H. B. Kim, E. C. Kim et al., Treatment failure due to emergence of resistance to carbapenem during therapy for Shewanella algae bacteremia, J Clin Microbiol, vol.44, pp.1172-1174, 2006.

A. B. Jousset, L. Dabos, R. A. Bonnin, D. Girlich, A. Potron et al., OXA-535, a Distantly Related OXA-48-Like Carbapenemase Antimicrobial Agents and Chemotherapy, aac.asm.org 5 on, vol.62, pp.1198-1216, 2018.

P. Glaser and T. Naas, CTX-M-15-producing Shewanella sp. clinical isolate expressing OXA-535, a chromosome-encoded OXA-48 variant, putative progenitor of the plasmid-encoded OXA-436, Antimicrob Agents Chemother, vol.62, pp.1879-1896, 2018.

L. Dabos, P. Bogaerts, R. A. Bonnin, A. Zavala, P. Sacré et al., Genetic and biochemical characterization of OXA-519, a novel OXA-48-like ?-lactamase, Antimicrob Agents Chemother, vol.62, pp.469-487, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02568064

D. Meziane-cherif, R. Bonnet, A. Haouz, P. Courvalin, Y. Hoyos-mallecot et al., Structural insights into the loss of penicillinase and the gain of ceftazidimase activities by OXA-145 ?-lactamase in Pseudomonas aeruginosa, Antimicrob Agents Chemother, vol.71, pp.818-835, 2016.

M. L. Verdonk, J. C. Cole, M. J. Hartshorn, C. W. Murray, and R. D. Taylor, Improved protein-ligand docking using GOLD, Proteins, vol.52, pp.609-623, 2003.

E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt et al., UCSF Chimera-a visualization system for exploratory research and analysis, J Comput Chem, vol.25, pp.1605-1612, 2014.

M. A. Toleman and T. R. Walsh, Combinatorial events of insertion sequences and ICE in Gram-negative bacteria, FEMS Microbiol Rev, vol.35, pp.912-935, 2011.

. Dabos, aac.asm.org 6 on, vol.62, pp.1198-1216, 2018.

, France 2 Bacteriology-Hygiene unit, Assistance Publique/Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France 3 Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-producing Enterobacteriaceae, EA7361 "Structure, dynamic, function and expression of broad spectrum ?-lactamases, vol.94275, p.33

P. M. Hawkey, Resistance to carbapenems, J Med Microbiol, vol.46, pp.451-455, 1997.

A. M. Queenan and K. Bush, Carbapenemases: the Versatile ?-Lactamases, Clin Microbiol Rev, vol.20, pp.440-58, 2007.

G. Peirano, P. A. Bradford, K. M. Kazmierczak, L. Chen, B. N. Kreiswirth et al., Importance of Clonal Complex 258 and IncFK2-like Plasmids among a Global Collection of Klebsiella pneumoniae with blaKPC, Antimicrob Agents Chemother, vol.61, pp.2610-2626, 2017.

S. Bratu, D. Landman, and R. Haag, Rapid Spread of Carbapenem-Resistant Klebsiella pneumoniae in New York City: A New Threat to Our Antibiotic Armamentarium, Arch Intern Med, vol.165, pp.1430-1435, 2005.

H. Yigit, A. M. Queenan, and G. J. Anderson, Novel Carbapenem-Hydrolyzing ?-Lactamase, KPC-1, from a Carbapenem-Resistant Strain of Klebsiella pneumoniae, Antimicrob Agents Chemother, vol.45, pp.1151-61, 2001.

T. Naas, S. Oueslati, and R. A. Bonnin, Beta-lactamase database (BLDB) -structure and function, Journal of Enzyme Inhibition and Medicinal Chemistry, vol.32, pp.917-926, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02119817

J. Alba, Y. Ishii, K. Thomson, E. S. Moland, and K. Yamaguchi, Kinetics Study of KPC-3, a Plasmid-Encoded Class A Carbapenem-Hydrolyzing ?-Lactamase, Antimicrob Agents Chemother, vol.49, pp.4760-4762, 2005.

C. Hidalgo-grass, G. Warburg, and V. Temper, KPC-9, a Novel Carbapenemase from Clinical Specimens in Israel, Antimicrob Agents Chemother, vol.56, pp.6057-6066, 2012.

T. L. Lamoureaux, H. Frase, N. T. Antunes, and S. B. Vakulenko, Antibiotic Resistance and Substrate Profiles of the Class A Carbapenemase KPC-6, Antimicrob Agents Chemother, vol.56, pp.6006-6014, 2012.

D. J. Wolter, P. M. Kurpiel, N. Woodford, M. Palepou, R. V. Goering et al., Phenotypic and Enzymatic Comparative Analysis of the Novel KPC Variant KPC-5 and Its Evolutionary Variants, KPC-2 and KPC-4, Antimicrob Agents Chemother, vol.53, pp.557-62, 2009.

S. C. Mehta, K. Rice, and T. Palzkill, Natural Variants of the KPC-2 Carbapenemase have Evolved Increased Catalytic Efficiency for Ceftazidime Hydrolysis at the Cost of Enzyme Stability Bonomo R, ed, PLOS Pathogens, vol.11, p.1004949, 2015.

R. K. Shields, M. H. Nguyen, E. G. Press, L. Chen, B. N. Kreiswirth et al., In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases, Antimicrob Agents Chemother, vol.61, pp.79-96, 2017.

D. M. Livermore, M. Warner, and D. Jamrozy, In Vitro Selection of Ceftazidime-Avibactam Resistance in Enterobacteriaceae with KPC-3 Carbapenemase, Antimicrob Agents Chemother, vol.59, pp.5324-5354, 2015.

M. J. Giddins, N. Macesic, and M. K. Annavajhala, Successive Emergence of Ceftazidime-Avibactam Resistance through Distinct Genomic Adaptations in blaKPC-2-Harboring Klebsiella pneumoniae Sequence Type 307 Isolates, Antimicrob Agents Chemother, vol.62, pp.2101-2118, 2018.

R. M. Humphries, S. Yang, and P. Hemarajata, First Report of Ceftazidime-Avibactam Resistance in a KPC-3-Expressing Klebsiella pneumoniae Isolate, Antimicrob Agents Chemother, vol.59, pp.6605-6612, 2015.

P. Gaibani, C. Campoli, and R. E. Lewis, In vivo evolution of resistant subpopulations of KPC-producing Klebsiella pneumoniae during ceftazidime/avibactam treatment, J Antimicrob Chemother, vol.73, pp.1525-1534, 2018.

R. K. Shields, B. A. Potoski, and G. Haidar, Clinical Outcomes, Drug Toxicity, and Emergence of Ceftazidime-Avibactam Resistance Among Patients Treated for Carbapenem-Resistant Enterobacteriaceae Infections, Clin Infect Dis, vol.63, pp.1615-1623, 2016.

R. P. Ambler, A. Coulson, and J. M. Frère, A standard numbering scheme for the class A ?-lactamases, Biochemical Journal, vol.276, pp.269-70, 1991.

R. Beyrouthy, F. Robin, and A. Lessene, MCR-1 and OXA-48 In Vivo Acquisition in KPC-Producing Escherichia coli after Colistin Treatment, Antimicrob Agents Chemother, p.61, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01639753

A. ?ali and T. L. Blundell, Comparative Protein Modelling by Satisfaction of Spatial Restraints, Journal of Molecular Biology, vol.234, pp.779-815, 1993.

O. A. Pemberton, X. Zhang, and Y. Chen, Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2), Journal of Medicinal Chemistry, vol.60, pp.3525-3555, 2017.

P. Nordmann, L. Poirel, and L. Dortet, Rapid Detection of Carbapenemase-producing Enterobacteriaceae, Emerg Infect Dis, vol.18, pp.1503-1510, 2012.

L. Dortet, A. Agathine, T. Naas, G. Cuzon, L. Poirel et al., Evaluation of the RAPIDEC® CARBA NP, the Rapid CARB Screen® and the Carba NP test for biochemical detection of carbapenemase-producing Enterobacteriaceae, J Antimicrob Chemother, vol.70, pp.3014-3036, 2015.

S. Bernabeu, L. Dortet, and T. Naas, Evaluation of the ?-CARBATM test, a colorimetric test for the rapid detection of carbapenemase activity in Gram-negative bacilli, J Antimicrob Chemother, vol.72, pp.1646-58, 2017.

P. Sa??ro?lu, U. Hasdemir, A. Gelmez, G. Aksu, B. Karatuna et al., Performance of "RESIST-3 O.K.N. K-SeT" immunochromatographic assay for the detection of OXA-48 like, KPC, and NDM carbapenemases in Klebsiella pneumoniae in Turkey, Brazilian Journal of Microbiology, 2018.

Y. Glupczynski, A. Jousset, and S. Evrard, Prospective evaluation of the OKN K-SeT assay, a new multiplex immunochromatographic test for the rapid detection of OXA-48-like, KPC and NDM carbapenemases, J Antimicrob Chemother, vol.72, pp.1955-60, 2017.

H. Boutal, A. Vogel, and S. Bernabeu, A multiplex lateral flow immunoassay for the rapid identification of NDM-, KPC-, IMP-and VIM-type and OXA-48-like carbapenemaseproducing Enterobacteriaceae, J Antimicrob Chemother, vol.73, pp.909-924, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02629307

L. Dortet, M. Fusaro, and T. Naas, Improvement of the Xpert Carba-R Kit for the Detection of Carbapenemase-Producing Enterobacteriaceae, Antimicrob Agents Chemother, vol.60, pp.3832-3839, 2016.

N. Stoesser, A. E. Sheppard, and G. Peirano, Genomic epidemiology of global Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli, Scientific Reports, vol.7, p.5917, 2017.

L. Dortet, S. Oueslati, K. Jeannot, D. Tandé, T. Naas et al., Genetic and Biochemical Characterization of OXA-405, an OXA-48-Type Extended-Spectrum ?-Lactamase without Significant Carbapenemase Activity, Antimicrob Agents Chemother, vol.59, pp.3823-3831, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01689515

L. Dortet, D. Tandé, and D. De-briel, MALDI-TOF for the rapid detection of carbapenemase-producing Enterobacteriaceae: comparison of the commercialized MBT STAR®-Carba IVD Kit with two in-house MALDI-TOF techniques and the RAPIDEC® CARBA NP, J Antimicrob Chemother. Available at, 2018.

P. Nordmann, G. Cuzon, and T. Naas, The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria, The Lancet Infectious Diseases, vol.9, pp.228-264, 2009.

. Anon, Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections -ScienceDirect, S1198743X14627026?via%3Dihub. Accessed, 2018.

G. Patel, S. Huprikar, S. H. Factor, S. G. Jenkins, and D. P. Calfee, Outcomes of Carbapenem-Resistant Klebsiella pneumoniae Infection and the Impact of Antimicrobial and Adjunctive Therapies, Infection Control & Hospital Epidemiology, vol.29, pp.1099-106, 2008.

T. Stachyra, P. Levasseur, and M. Péchereau, In vitro activity of the ?-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases, J Antimicrob Chemother, vol.64, pp.326-335, 2009.

R. K. Shields, L. Chen, and S. Cheng, Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne blaKPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections, Antimicrob Agents Chemother, vol.61, 2017.

P. Artimo, M. Jonnalagedda, and K. Arnold, SIB bioinformatics resource portal, vol.40, pp.597-603, 2012.

M. L. Verdonk, J. C. Cole, M. J. Hartshorn, C. W. Murray, and R. D. Taylor, Improved protein-ligand docking using GOLD, Proteins: Structure, Function, and Bioinformatics, vol.52, pp.609-632, 2003.

E. F. Pettersen, T. D. Goddard, and C. C. Huang, UCSF Chimera-A visualization system for exploratory research and analysis, Journal of Computational Chemistry, vol.25, pp.1605-1617

R. A. Bonomo, b-Lactamases: a focus on current challenges, Cold Spring Harb Perspect Med, vol.7, p.25239, 2017.

P. Nordmann, T. Naas, and L. Poirel, Global spread of Carbapenemase-producing Enterobacteriaceae, Emerg Infect Dis, vol.17, pp.1791-1799, 2011.

T. Naas, L. Dortet, and B. I. Iorga, Structural and functional aspects of class A carbapenemases, Curr Drug Targets, vol.17, pp.1006-1034, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02135284

B. Liu and M. Pop, ARDB -Antibiotic Resistance Genes Database, Nucleic Acids Res, vol.37, pp.443-450, 2009.

Q. K. Thai, F. B?-os, and J. Pleiss, The Lactamase Engineering Database: a critical survey of TEM sequences in public databases, BMC Genomics, vol.10, p.390, 2009.

Q. K. Thai, J. Pleiss, and . Shv-lactamase, Engineering Database: a reconciliation tool for SHV b-lactamases in public databases, BMC Genomics, vol.11, p.563, 2010.

M. Widmann, J. Pleiss, and P. Oelschlaeger, Systematic analysis of metallo-b-lactamases using an automated database, Antimicrob Agents Chemother, vol.56, pp.3481-91, 2012.

A. G. Mcarthur, N. Waglechner, and F. Nizam, The comprehensive antibiotic resistance database, Antimicrob Agents Chemother, vol.57, pp.3348-57, 2013.

M. Danishuddin, H. Baig, M. Kaushal, L. Khan, and A. U. , BLAD: a comprehensive database of widely circulated b-lactamases, Bioinformatics, vol.29, pp.2515-2531, 2013.

A. Srivastava, N. Singhal, and M. Goel, CBMAR: a comprehensive b-lactamase molecular annotation resource, Database (Oxford), p.111, 2014.

F. Sievers, A. Wilm, and D. Dineen, Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega, Mol Syst Biol, vol.7, p.539, 2011.

A. Priyam, B. J. Woodcroft, and V. Rai, Sequenceserver: a modern graphical user interface for custom BLAST databases, p.33142, 2015.

R. Agarwala, T. Barrett, and J. Beck, Database resources of the National Center for Biotechnology Information, Nucleic Acids Res, vol.44, pp.7-19, 2016.

H. M. Berman, J. Westbrook, and Z. Feng, The Protein Data Bank, Nucleic Acids Res, vol.28, pp.235-277, 2000.

, Bogdan I. Iorga, vol.2

, AP-HP, vol.7361

M. Paris-sud, L. Labex, and L. Kremlin-bicêtre, France 2 Institut de Chimie des Substances Naturelles, CNRS UPR 2301

L. K. Logan and R. A. Weinstein, The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace, J Infect Dis, vol.215, pp.28-36, 2017.

T. J. Gniadek, K. C. Carroll, and P. J. Simner, Carbapenem-Resistant Non-Glucose-Fermenting Gram-Negative Bacilli: the Missing Piece to the Puzzle, J Clin Microbiol, vol.54, pp.1700-1710, 2016.

B. Albiger, C. Glasner, M. J. Struelens, H. Grundmann, and D. L. Monnet, European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) working group. Carbapenemaseproducing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, Euro Surveill, vol.20, issue.45, 2015.

L. Dortet, G. Cuzon, V. Ponties, and P. Nordmann, Trends in carbapenemase-producing Enterobacteriaceae, Euro Surveill, vol.22, issue.6, p.30461, 2012.

L. Poirel, T. Naas, and P. Nordmann, Diversity, epidemiology, and genetics of class D ?-lactamases, Antimicrob. Agents Chemother, vol.54, pp.24-38, 2010.

D. Aubert, T. Naas, C. Héritier, L. Poirel, and P. Nordmann, Functional characterization of IS1999, an IS4 family element involved in mobilization and expression of beta-lactam resistance genes, J Bacteriol, vol.188, pp.6506-6520, 2006.

T. Naas, S. Oueslati, R. A. Bonnin, M. L. Dabos, A. Zavala et al., Beta-lactamase database (BLDB) -structure and function, J Enzyme Inhib Med Chem, vol.32, pp.917-919, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02119817

F. Couture, J. Lachapelle, and R. C. Levesque, Phylogeny of LCR-1 and OXA-5 with class A and class D beta-lactamases, Mol Microbiol, vol.6, pp.1693-1705, 1992.

C. Heritier, L. Poirel, D. Aubert, and P. Nordmann, Genetic and functional analysis of the chromosome-encoded carbapenem-hydrolyzing oxacillinase OXA-40 of Acinetobacter baumannii, Antimicrob Agents Chemother, vol.47, pp.268-273, 2003.

J. D. Docquier, V. Calderone, D. Luca, F. Benvenuti, M. Giuliani et al., Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases, Chem Biol, vol.16, pp.540-547, 2009.

S. Oueslati, P. Nordmann, and L. Poirel, Heterogeneous hydrolytic features for OXA-48-like ?-lactamases, J Antimicrob Chemother, vol.70, pp.1059-63, 2015.

Y. Hoyos-mallecot, T. Naas, R. A. Bonnin, R. Patino, P. Glaser et al., OXA-244-Producing Escherichia coli Isolates, a Challenge for Clinical Microbiology Laboratories, Antimicrob Agents Chemother, vol.61, pp.818-835, 2017.

L. Dortet, S. Oueslati, K. Jeannot, D. Tandé, T. Naas et al., Genetic and biochemical characterization of OXA-405, an OXA-48-type extended-spectrum ?-lactamase without significant carbapenemase activity, Antimicrob Agents Chemother, vol.59, pp.3823-3831, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01689515

L. Poirel, A. Potron, P. Nordmann, and . Oxa, , p.48

. Oueslati, like carbapenemases: the phantom menace, J. Antimicrob. Chemother, vol.67, pp.1597-1606, 2012.

A. Potron, L. Poirel, and P. Nordmann, Origin of OXA-181, an emerging carbapenem-hydrolyzing oxacillinase, as a chromosomal gene in Shewanella xiamenensis, Antimicrob Agents Chemother, vol.55, pp.4405-4412, 2011.

M. Tacão, A. Correia, and I. Henriques, Environmental Shewanella xiamenensis strains that carry blaOXA-48 or blaOXA-204 genes: additional proof for blaOXA-48-like gene origin, Antimicrob Agents Chemother, vol.57, pp.6399-400, 2013.

M. Xu, Y. Fang, J. Liu, X. Chen, G. Sun et al., Draft genome sequence of Shewanella decolorationis S12, a dye-degrading bacterium isolated from a wastewater treatment plant

, Genome Announc, vol.1, pp.993-00913, 2013.

Y. Li, I. S. Ng, X. Zhang, and N. Wang, Draft genome sequence of the dye-decolorizing and nanowireproducing bacterium Shewanella xiamenensis BC01, Genome Announc, vol.2, pp.721-00714, 2014.

D. H. Huson and C. Scornavacca, Dendroscope 3: An interactive tool for rooted phylogenetic trees and networks, Syst. Biol, vol.6, pp.1061-1067, 2012.
URL : https://hal.archives-ouvertes.fr/hal-02154987

M. A. Larkin, G. Blackshields, N. P. Brown, R. Chenna, P. A. Mcgettigan et al., Clustal W and Clustal X version 2.0, Bioinformatics, vol.23, pp.2947-2948, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00206210

, Chemoinformatics Tanimoto similarities were computed using CACTVS Chemoinformatics Toolkit v3.409 (Xemistry

D. Bishop-bailey, FXR as a novel therapeutic target for vascular disease, Drug News Perspect, vol.17, issue.8, pp.499-504, 2004.

T. Claudel, E. Sturm, F. Kuipers, and B. Staels, The farnesoid X receptor: a novel drug target?, Expert Opin Investig Drugs, vol.13, issue.9, pp.1135-1148, 2004.

R. Pellicciari, G. Costantino, and S. Fiorucci, Farnesoid X receptor: from structure to potential clinical applications, J Med Chem, vol.48, issue.17, pp.5383-5403, 2005.

S. Westin, R. A. Heyman, and R. Martin, FXR, a therapeutic target for bile acid and lipid disorders, Mini Rev Med Chem, vol.5, issue.8, pp.719-727, 2005.

S. Y. Cai and J. L. Boyer, FXR: a target for cholestatic syndromes?, Expert Opin Ther Targets, vol.10, issue.3, pp.409-421, 2006.

F. Y. Lee, H. Lee, M. L. Hubbert, P. A. Edwards, and Y. Zhang, FXR, a multipurpose nuclear receptor, Trends Biochem Sci, vol.31, issue.10, pp.572-580, 2006.

B. Cariou and B. Staels, FXR: a promising target for the metabolic syndrome?, Trends Pharmacol Sci, vol.28, issue.5, pp.236-243, 2007.

Y. D. Wang, W. D. Chen, and W. Huang, FXR, a target for different diseases, Histol Histopathol, vol.23, issue.5, pp.621-627, 2008.

A. Zimber and C. Gespach, Bile acids and derivatives, their nuclear receptors FXR, PXR and ligands: role in health and disease and their therapeutic potential, Anticancer Agents Med Chem, vol.8, issue.5, pp.540-563, 2008.

M. L. Crawley, Farnesoid X receptor modulators: a patent review, Expert Opin Ther Pat, vol.20, issue.8, pp.1047-1057, 2010.

S. Fiorucci, A. Mencarelli, E. Distrutti, G. Palladino, and S. Cipriani, Targetting farnesoid-X-receptor: from medicinal chemistry to disease treatment, Curr Med Chem, vol.17, issue.2, pp.139-159, 2010.

A. Mencarelli and S. Fiorucci, FXR an emerging therapeutic target for the treatment of atherosclerosis, J Cell Mol Med, vol.14, issue.1-2, pp.79-92, 2010.

J. S. Teodoro, A. P. Rolo, and C. M. Palmeira, Hepatic FXR: key regulator of whole-body energy metabolism, Trends Endocrinol Metab, vol.22, issue.11, pp.458-466, 2011.

L. Adorini, M. Pruzanski, and D. Shapiro, Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis, Drug Discov Today, vol.17, pp.988-997, 2012.

S. Fiorucci, A. Mencarelli, E. Distrutti, and A. Zampella, Farnesoid X receptor: from medicinal chemistry to clinical applications, Future Med Chem, vol.4, issue.7, pp.877-891, 2012.

S. Fiorucci, A. Zampella, and E. Distrutti, Development of FXR, PXR and CAR agonists and antagonists for treatment of liver disorders, Curr Top Med Chem, vol.12, issue.6, pp.605-624, 2012.

S. Pronk, S. Pall, R. Schulz, P. Larsson, P. Bjelkmar et al., GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit, Bioinformatics, vol.29, issue.7, pp.845-854, 2013.

A. Carotti, M. Marinozzi, C. Custodi, B. Cerra, R. Pellicciari et al., Beyond bile acids: targeting Farnesoid X Receptor (FXR) with natural and synthetic ligands, Curr Top Med Chem, vol.14, pp.2129-2142, 2014.

S. Fiorucci, E. Distrutti, P. Ricci, V. Giuliano, A. Donini et al., Targeting FXR in cholestasis: hype or hope, Expert Opin Ther Targets, vol.18, issue.12, pp.1449-1459, 2014.

C. Gege, O. Kinzel, C. Steeneck, A. Schulz, and C. Kremoser, Knocking on FXR's door: the "hammerhead"-structure series of FXR agonists: amphiphilic isoxazoles with potent in vitro and in vivo activities, Curr Top Med Chem, vol.14, pp.2143-2158, 2014.

H. Huang, Y. Xu, J. Zhu, and J. Li, Recent advances in non-steroidal FXR antagonists development for therapeutic applications, Curr Top Med Chem, vol.14, pp.2175-2187, 2014.

C. Lamers, M. Schubert-zsilavecz, and D. Merk, Medicinal chemistry and pharmacological effects of Farnesoid X Receptor (FXR) antagonists, Curr Top Med Chem, vol.14, pp.2188-2205, 2014.

A. H. Ali, E. J. Carey, and K. D. Lindor, Recent advances in the development of farnesoid X receptor agonists, Ann Transl Med, vol.3, issue.1, p.5, 2015.

R. M. Carr and A. E. Reid, FXR agonists as therapeutic agents for non-alcoholic fatty liver disease, Curr Atheroscler Rep, vol.17, issue.4, p.500, 2015.

I. Koutsounas, S. Theocharis, I. Delladetsima, E. Patsouris, and C. Giaginis, Farnesoid X receptor in human metabolism and disease: the interplay between gene polymorphisms, clinical phenotypes and disease susceptibility, Expert Opin Drug Metab Toxicol, vol.11, issue.4, pp.523-532, 2015.

A. J. Sanyal, Use of farnesoid X receptor agonists to treat nonalcoholic fatty liver disease, Dig Dis, vol.33, issue.3, pp.426-432, 2015.

V. Sepe, E. Distrutti, S. Fiorucci, and A. Zampella, Farnesoid X receptor modulators (2011-2014): a patent review, Expert Opin Ther Pat, vol.25, issue.8, pp.885-896, 2015.

V. Sepe, E. Distrutti, V. Limongelli, S. Fiorucci, and A. Zampella, Steroidal scaffolds as FXR and GPBAR1 ligands: from chemistry to therapeutical application, Future Med Chem, vol.7, issue.9, pp.1109-1135, 2015.

A. S. Alawad and C. Levy, FXR agonists: from bench to bedside, a guide for clinicians, Dig Dis Sci, vol.61, issue.12, pp.3395-3404, 2016.

C. D. De-magalhaes-filho, M. Downes, and R. M. Evans, Farnesoid X Receptor an emerging target to combat obesity, Dig Dis, vol.35, issue.3, pp.185-190, 2017.

S. Feng, M. Yang, Z. Zhang, Z. Wang, D. Hong et al., Identification of an N-oxide pyridine GW4064 analog as a potent FXR agonist, Bioorg Med Chem Lett, vol.19, issue.9, pp.2595-2598, 2009.

H. G. Richter, G. M. Benson, K. H. Bleicher, D. Blum, E. Chaput et al., Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties, Bioorg Med Chem Lett, vol.21, issue.4, pp.1134-1140, 2011.

H. G. Richter, G. M. Benson, D. Blum, E. Chaput, S. Feng et al., Discovery of novel and orally active FXR agonists for the potential treatment of dyslipidemia & diabetes, Bioorg Med Chem Lett, vol.21, issue.1, pp.191-194, 2011.

H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat et al., The Protein Data Bank, Nucleic Acids Res, vol.28, issue.1, pp.235-242, 2000.

A. Sali and T. L. Blundell, Comparative protein modelling by satisfaction of spatial restraints, J Mol Biol, vol.234, issue.3, pp.779-815, 1993.

M. L. Verdonk, J. C. Cole, M. J. Hartshorn, C. W. Murray, and R. D. Taylor, Improved protein-ligand docking using GOLD, Proteins Struct Funct Bioinf, vol.52, issue.4, pp.609-623, 2003.

G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew et al., AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, J Comput Chem, vol.30, issue.16, pp.2785-2791, 2009.

E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt et al., UCSF Chimera: a visualization system for exploratory research and analysis, J Comput Chem, vol.25, issue.13, pp.1605-1612, 2004.

O. Trott and A. J. Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J Comput Chem, vol.31, issue.2, pp.455-461, 2010.

G. A. Kaminski, R. A. Friesner, J. Tirado-rives, and W. L. Jorgensen, Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides, J Phys Chem B, vol.105, issue.28, pp.6474-6487, 2001.

M. J. Robertson, J. Tirado-rives, and W. L. Jorgensen, Improved peptide and protein torsional energetics with the OPLS-AA force field, J Chem Theory Comput, vol.11, issue.7, pp.3499-3509, 2015.

V. Gapsys, S. Michielssens, D. Seeliger, and B. L. De-groot, pmx: Automated protein structure and topology generation for alchemical perturbations, J Comput Chem, vol.36, issue.5, pp.348-354, 2015.

V. Gapsys, S. Michielssens, J. H. Peters, B. L. De-groot, and H. Leonov, Calculation of binding free energies, Methods Mol Biol, vol.1215, pp.173-209, 2015.

V. Gapsys, S. Michielssens, D. Seeliger, and B. L. De-groot, Accurate and rigorous prediction of the changes in protein free energies in a large-scale mutation scan, Angew Chem, vol.55, issue.26, pp.7364-7368, 2016.

G. Surpateanu and B. I. Iorga, Evaluation of docking performance in a blinded virtual screening of fragment-like trypsin inhibitors, J Comput Aided Mol Des, vol.26, issue.5, pp.595-601, 2012.
URL : https://hal.archives-ouvertes.fr/hal-02377117

C. Colas and B. I. Iorga, Virtual screening of the SAMPL4 blinded HIV integrase inhibitors dataset, J Comput Aided Mol Des, vol.28, issue.4, pp.455-462, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02377128

V. Y. Martiny, F. Martz, E. Selwa, and B. I. Iorga, Blind pose prediction, scoring, and affinity ranking of the CSAR 2014 dataset, J Chem Inf Model, vol.56, issue.6, pp.996-1003, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02135548

E. Selwa, V. Y. Martiny, and B. I. Iorga, Molecular docking performance evaluated on the D3R Grand Challenge 2015 druglike ligand datasets, J Comput Aided Mol Des, vol.30, issue.9, pp.829-839, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02377131

J. Grunenberg and G. Licari, Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibioticribosome complex supervised by experiment and electronic structure methods, Beilstein J Org Chem, vol.12, pp.415-428, 2016.

, with a tandem tripeptide insertion, Biochemistry, vol.38, pp.10256-61

L. Dabos, J. E. Raczynska, P. Bogaerts, A. Zavala, R. A. Bonnin et al., Structural plasticity of class D ?-lactamases: OXA-517, a novel OXA-48 variant with carbapenem and expanded spectrum cephalosporin hydrolysis, 2018.

L. Dabos, A. Zavala, R. A. Bonnin, O. Beckstein, P. Retailleau et al., Substrate specificity of OXA-48 modified by ?5-?6 loop replacement, 2018.

L. Dabos, A. Zavala, L. Dortet, R. A. Bonnin, O. Beckstein et al., Role of the loop ?5-?6 in the substrate specificity of OXA-48, 2018.

L. Dortet, G. Cuzon, V. Ponties, and P. Nordmann, Trends in carbapenemase-producing Enterobacteriaceae, Euro Surveill, vol.22, p.30461, 2012.

J. R. Horn and B. K. Shoichet, Allosteric Inhibition Through Core Disruption, J. Mol. Biol, vol.336, pp.1283-1291, 2004.

K. Kaitany, N. Klinger, C. M. June, M. E. Ramey, R. A. Bonomo et al., Structures of the class D Carbapenemases OXA-23 and OXA-146: mechanistic basis of activity against carbapenems, extended-spectrum cephalosporins, and aztreonam, Antimicrob. Agents Chemother, vol.57, pp.4848-55, 2013.

A. Kakasis and G. Panitsa, Bacteriophage therapy as an alternative treatment for human infections. A comprehensive review, Int. J. Antimicrob. Agents, 2018.

S. D. Kotsakis, L. S. Tzouvelekis, E. Petinaki, E. Tzelepi, and V. Miriagou, Effects of the Val211Gly substitution on molecular dynamics of the CMY-2 cephalosporinase: Implications on hydrolysis of expanded-spectrum cephalosporins, Proteins Struct. Funct. Bioinforma, vol.79, pp.3180-3192, 2011.

T. Naas, S. Oueslati, R. A. Bonnin, M. L. Dabos, A. Zavala et al., Beta-lactamase database (BLDB) -structure and function, J. Enzyme Inhib. Med. Chem, vol.32, pp.917-919, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02119817

J. O'neill, Antimicrobial resistance: tackling a crisis for the health and wealth of nations, Rev. Antimicrob. Resist, vol.20, pp.1-16, 2014.

L. Poirel, M. Castanheira, A. Carrër, C. P. Rodriguez, R. N. Jones et al., OXA-163, an OXA-48-Related Class D ?-Lactamase with Extended Activity Toward Expanded-Spectrum Cephalosporins, Antimicrob. Agents Chemother, vol.55, pp.2546-2551, 2011.

R. K. Shields, L. Chen, S. Cheng, K. D. Chavda, E. G. Press et al., Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne bla KPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections, Antimicrob. Agents Chemother, p.61, 2017.

A. Zavala, L. Dabos, P. Retailleau, S. Oueslati, T. Naas et al., X-ray crystallography of synthetic mutant OXA-48 P217del: nitrate as a class D ?-lactamase inhibitor, 2018.