M. Maurin and M. Gyuranecz, Tularaemia: clinical aspects in Europe, Lancet Infect. Dis, vol.16, pp.113-124, 2016.

K. L. Meibom and A. Charbit, The unraveling panoply of Francisella tularensis virulence attributes, Curr. Opin. Microbiol, vol.13, pp.11-17, 2010.

J. W. Conlan, W. Chen, H. Shen, A. Webb, and R. Kuolee, Experimental tularemia in mice challenged by aerosol or intradermally with virulent strains of Francisella tularensis: bacteriologic and histopathologic studies, Microb. Pathog, vol.34, pp.239-248, 2003.

M. Maurin, Francisella tularensis as a potential agent of bioterrorism?, Expert Rev. Anti Infect. Ther, vol.13, pp.141-144, 2015.

P. C. Oyston, A. Sjostedt, and R. W. Titball, Tularaemia: bioterrorism defence renews interest in Francisella tularensis, Nat. Rev. Microbiol, vol.2, pp.967-978, 2004.

N. M. Perez and G. Ramakrishnan, The reduced genome of the Francisella tularensis live vaccine strain (LVS) encodes two iron acquisition systems essential for optimal growth and virulence, PLoS ONE, vol.9, p.93558, 2014.

G. Ramakrishnan, B. Sen, and R. Johnson, Paralogous outer membrane proteins mediate uptake of different forms of iron and synergistically govern virulence in Francisella tularensis tularensis, J. Biol. Chem, vol.287, pp.25191-25202, 2012.

H. Lindgren, Iron content differs between Francisella tularensis subspecies tularensis and subspecies holarctica strains and correlates to their susceptibility to H(2)O(2)-induced killing, Infect. Immun, vol.79, pp.1218-1224, 2011.

G. Ramakrishnan, A. Meeker, and B. Dragulev, fslE is necessary for siderophore-mediated iron acquisition in Francisella tularensis Schu S4, J. Bacteriol, vol.190, pp.5353-5361, 2008.

X. Pan, B. Tamilselvam, E. J. Hansen, and S. Daefler, Modulation of iron homeostasis in macrophages by bacterial intracellular pathogens, BMC Microbiol, vol.10, p.64, 2010.

C. J. Carrano, Coordination chemistry of the carboxylate type siderophore rhizoferrin: the iron(III) complex and its metal analogs, Inorg. Chem, vol.35, pp.6429-6436, 1996.

J. T. Sullivan, E. F. Jeffery, J. D. Shannon, and G. Ramakrishnan, Characterization of the siderophore of Francisella tularensis and role of fslA in siderophore production, J. Bacteriol, vol.188, pp.3785-3795, 2006.

T. D. Wehrly, Intracellular biology and virulence determinants of Francisella tularensis revealed by transcriptional profiling inside macrophages, Cell Microbiol, vol.11, pp.1128-1150, 2009.

K. Deng, R. J. Blick, W. Liu, and E. J. Hansen, Identification of Francisella tularensis genes affected by iron limitation, Infect. Immun, vol.74, pp.4224-4236, 2006.

K. Kiss, W. Liu, J. F. Huntley, M. V. Norgard, and E. J. Hansen, Characterization of fig operon mutants of Francisella novicida U112, FEMS Microbiol. Lett, vol.285, pp.270-277, 2008.

M. F. Fillat, The FUR (ferric uptake regulator) superfamily: diversity and versatility of key transcriptional regulators, Arch. Biochem. Biophys, vol.546, pp.41-52, 2014.

C. Doi,

S. W. Seo, Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli, Nat. Commun, vol.5, p.4910, 2014.

D. Touati, Iron and oxidative stress in bacteria, Arch. Biochem. Biophys, vol.373, pp.1-6, 2000.

E. Ughetto, An original case of Francisella tularensis subsp. holarctica bacteremia after a near-drowning accident, Infect. Dis. (Lond.), vol.47, pp.588-590, 2015.

J. Perard, Quaternary structure of Fur proteins, a new subfamily of tetrameric proteins, Biochemistry, vol.55, pp.1503-1515, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01291325

S. Vitale, A ZnS(4) structural zinc site in the Helicobacter pylori ferric uptake regulator, Biochemistry, vol.48, pp.5582-5591, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00936388

C. Dian, The structure of the Helicobacter pylori ferric uptake regulator Fur reveals three functional metal binding sites, Mol. Microbiol, vol.79, pp.1260-1275, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00936385

P. I. Watnick, T. Eto, H. Takahashi, and S. B. Calderwood, Purification of Vibrio cholerae fur and estimation of its intracellular abundance by antibody sandwich enzyme-linked immunosorbent assay, J. Bacteriol, vol.179, pp.243-247, 1997.

M. Zheng, B. Doan, T. D. Schneider, and G. Storz, OxyR and SoxRS regulation of fur, J. Bacteriol, vol.181, pp.4639-4643, 1999.

S. A. Mills and M. A. Marletta, Metal binding characteristics and role of iron oxidation in the ferric uptake regulator from Escherichia coli, Biochemistry, vol.44, pp.13553-13559, 2005.

E. Krissinel and K. Henrick, Inference of macromolecular assemblies from crystalline state, J. Mol. Biol, vol.372, pp.774-797, 2007.

E. Pohl, Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator, Mol. Microbiol, vol.47, pp.903-915, 2003.

A. Tiss, O. Barre, I. Michaud-soret, and E. Forest, Characterization of the DNA-binding site in the ferric uptake regulator protein from Escherichia coli by UV cross-linking and mass spectrometry, FEBS Lett, vol.579, pp.5454-5460, 2005.

Z. Deng, Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator, Nat. Commun, vol.6, p.7642, 2015.

B. A. Gilston, Structural and mechanistic basis of zinc regulation across the E. coli Zur regulon, PLoS Biol, vol.12, p.1001987, 2014.

I. Stojiljkovic, A. J. Baumler, and K. Hantke, Fur regulon in Gram-negative bacteria-identification and characterization of new iron-regulated Escherichia coli genes by a, Fur Titration Assay, vol.236, pp.271-271, 1994.

D. Franke and D. I. Svergun, DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering, J. Appl. Crystallogr, vol.42, pp.342-346, 2009.

G. Porcheron and C. M. Dozois, Interplay between iron homeostasis and virulence: Fur and RyhB as major regulators of bacterial pathogenicity, Vet. Microbiol, vol.179, pp.2-14, 2015.
URL : https://hal.archives-ouvertes.fr/pasteur-01352636

S. Mathieu, From peptide aptamers to inhibitors of FUR, bacterial transcriptional regulator of iron homeostasis and virulence, ACS Chem. Biol, vol.11, pp.2519-2528, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02008298

M. Maurin, I. Pelloux, J. P. Brion, J. N. Del-bano, and A. Picard, Human tularemia in France, Clin. Infect. Dis, vol.53, pp.133-141, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00993402

E. D. Lovullo, C. R. Molins-schneekloth, H. P. Schweizer, and M. S. Pavelka, Single-copy chromosomal integration systems for Francisella tularensis, Microbiology, vol.155, pp.1152-1163, 2009.

W. Kabsch and . Xds, Acta Crystallogr D, vol.66, pp.125-132, 2010.

P. D. Adams, PHENIX: a comprehensive Python-based system for macromolecular structure solution, Acta Crystallogr D, vol.66, pp.213-221, 2010.

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

A. A. Vagin, REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its use, Acta Crystallogr D, vol.60, pp.2184-2195, 2004.

M. D. Winn, Overview of the CCP4 suite and current developments, Acta Crystallogr D, vol.67, pp.235-242, 2011.

A. Vagin and A. Teplyakov, MOLREP: an automated program for molecular replacement, J. Appl. Crystallogr, vol.30, pp.1022-1025, 1997.

V. B. Chen, MolProbity: all-atom structure validation for macromolecular crystallography, Acta Crystallogr D, vol.66, pp.12-21, 2010.

R. P. Joosten, F. Long, G. N. Murshudov, and A. Perrakis, The PDB_REDO server for macromolecular structure model optimization, IUCrJ, vol.1, pp.213-220, 2014.

M. V. Petoukhov, New developments in the program package for smallangle scattering data analysis, J. Appl. Crystallogr, vol.45, p.350, 2012.

P. V. Konarev, V. V. Volkov, A. V. Sokolova, M. H. Koch, and D. I. Svergun, PRIMUS: a Windows PC-based system for small-angle scattering data analysis, J. Appl. Crystallogr, vol.36, pp.1277-1282, 2003.

V. V. Volkov and D. I. Svergun, Uniqueness of ab initio shape determination in small-angle scattering, J. Appl. Crystallogr, vol.36, pp.860-864, 2003.

M. B. Kozin and D. I. Svergun, Automated matching of high-and lowresolution structural models, J. Appl. Crystallogr, vol.34, pp.33-41, 2001.

B. R. Brooks, CHARMM: a program for macromolecular energy, minimization, and dynamics calculations, J. Comp. Chem, vol.4, pp.187-217, 1983.

M. J. Abraham, GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX, vol.1, issue.11, pp.19-25, 2015.

N. Schmid, Definition and testing of the GROMOS force-field versions 54A7 and 54B7, Eur. Biophys. J, vol.40, pp.843-856, 2011.

H. J. Berendsen, J. P. Postma, W. F. Van-gunsteren, and J. Hermans, Interaction Models for Water in Relation to Protein Hydration, pp.331-342, 1981.

S. Kumar, J. M. Rosenberg, D. Bouzida, R. H. Swendsen, and P. A. Kollman, The weighted histogram analysis method for free energy calculations on biomolecules. I. The method, J. Comput. Chem, vol.13, pp.1011-1021, 1992.

J. S. Hub, B. L. De-groot, and D. Van-der-spoel, GROMACS g_wham A free weighted histogram analysis implementation including robust error and autocorrelation estimates, J. Chem. Theory Comput, vol.6, p.3713, 2010.

R. , R: A Language and Environment for Statistical Computing, 2008.

L. Pecqueur, Structural changes of Escherichia coli ferric uptake regulator during metal-dependent dimerization and activation explored by NMR and Xray crystallography, J. Biol. Chem, vol.281, pp.21286-21295, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00381824

M. Maurin, I. Pelloux, J. P. Brion, J. N. Del-bano, and A. Picard, Human tularemia in France, Clin Infect Dis, vol.53, pp.133-174, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00993402

E. D. Lovullo, C. R. Molins-schneekloth, H. P. Schweizer, M. S. Pavelka, and . Jr, Singlecopy chromosomal integration systems for Francisella tularensis, Microbiology, vol.155, pp.1152-63, 2009.

E. D. Lovullo, L. A. Sherrill, M. S. Pavelka, and . Jr, Improved shuttle vectors for Francisella tularensis genetics, FEMS Microbiol Lett, vol.291, pp.95-102, 2009.

J. Perard, New Subfamily of Tetrameric Proteins. Biochemistry, vol.55, pp.1503-1518, 2016.

L. Pecqueur, Structural changes of Escherichia coli ferric uptake regulator during metal-dependent dimerization and activation explored by NMR and X-ray crystallography, J Biol Chem, vol.281, pp.21286-95, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00381824

E. Pohl, Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator, Mol Microbiol, vol.47, pp.903-918, 2003.

C. Dian, The structure of the Helicobacter pylori ferric uptake regulator Fur reveals three functional metal binding sites, Mol Microbiol, vol.79, pp.1260-75, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00936385

Z. Deng, Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator, Nat Commun, vol.6, p.7642, 2015.

M. J. Abraham, GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX, vol.1, issue.11, pp.19-25, 2015.

N. Schmid, Definition and testing of the GROMOS force-field versions 54A7 and 54B7, Eur Biophys J, vol.40, pp.843-56, 2011.

B. R. Brooks, CHARMM: a program for macromolecular energy, minimization, and dynamics calculations, J. Comp. Chem, vol.4, pp.187-217, 1983.

H. J. Berendsen, J. P. Postma, A. Dinola, and J. R. Haak, Molecular dynamics with coupling to an external bath, J. Chem. Phys, vol.81, pp.3684-3690, 1984.

M. Parrinello and A. Rahman, Polymorphic transitions in single crystals: A new molecular dynamics method, J. Appl. Phys, vol.52, pp.7182-7190, 1981.

R. , R: A language and environment for statistical computing, 2008.

N. Abed, M. Bickle, B. Mari, M. Schapira, R. Sanjuan-españa et al., A Comparative Analysis of Perturbations Caused by a Gene Knock-out, a Dominant Negative Allele, and a Set of Peptide Aptamers, Molecular & Cellular Proteomics, vol.6, pp.2110-2121, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00315657

M. J. Abraham, T. Murtola, R. Schulz, S. Pll, J. C. Smith et al., GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, In: SoftwareX, vol.12, pp.2352-7110, 2015.

L. A. Achenbach and . Yang, The fur gene from Klebsiella pneumoniae: characterization, genomic organization and phylogenetic analysis, In: Gene, vol.185, pp.378-1119, 1997.

P. D. Adams, PHENIX: a comprehensive Python-based system for macromolecular structure solution, In: Acta crystallographica. Section D, Biological crystallography, vol.66, pp.213-221, 2010.

P. Alamuri, N. Mehta, A. Burk, and R. J. Maier, Regulation of the Helicobacter pylori FeS cluster synthesis protein NifS by iron, oxidative stress conditions, and fur, In: Journal of bacteriology, vol.188, issue.14, pp.5325-5330, 2006.

H. K. Allen, J. Donato, H. H. Wang, K. A. Cloud-hansen, J. Davies et al., Call of the wild: antibiotic resistance genes in natural environments, Nature reviews. Microbiology, vol.8, pp.1740-1534, 2010.

E. W. Althaus, C. E. Outten, K. E. Olson, T. V. Cao, and . O'halloran, The ferric uptake regulation (Fur) repressor is a zinc metalloprotein, Biochemistry, vol.38, pp.6559-6569, 1999.

R. I. Aminov and R. I. Mackie, Evolution and ecology of antibiotic resistance genes, In: FEMS microbiology letters, vol.271, issue.2, pp.147-161, 2007.

A. D. Anbar, Oceans. Elements and evolution, pp.1095-9203, 2008.

S. C. Andrews, A. K. Robinson, and F. Rodríguez-quiñones, Bacterial iron homeostasis, In: FEMS microbiology reviews, vol.27, issue.2-3, pp.168-6445, 2003.

E. S. Arnér and . Holmgren, Physiological functions of thioredoxin and thioredoxin reductase, European journal of biochemistry, vol.267, pp.14-2956, 2000.

S. S. Athavale, A. S. Petrov, C. Hsiao, D. Watkins, C. D. Prickett et al., RNA folding and catalysis mediated by iron (II), In: PloS one, vol.7, 2012.

A. Bagg and J. B. Neilands, Ferric uptake regulation protein acts as a repressor, employing iron (II) as a cofactor to bind the operator of an iron transport operon in Escherichia coli, In: Biochemistry, vol.26, pp.6-2960, 1987.

N. Baichoo and J. D. Helmann, Recognition of DNA by Fur: a reinterpretation of the Fur box consensus sequence, In: Journal of bacteriology, vol.184, pp.21-9193, 2002.

K. S. Baker, E. Burnett, H. Mcgregor, A. Deheer-graham, C. Boinett et al., The Murray collection of pre-antibiotic era Enterobacteriacae: a unique research resource, In: Genome medicine, vol.7, pp.1756-994, 2015.

M. F. Barber and N. C. Elde, Escape from bacterial iron piracy through rapid evolution of transferrin, In: Science, pp.1095-9203, 2014.

M. F. Barber and N. C. Elde, Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy, In: Trends in genetics : TIG, pp.168-9525, 2015.

M. Barlow and B. G. Hall, Phylogenetic analysis shows that the OXA beta-lactamase genes have been on plasmids for millions of years, In: Journal of molecular evolution, vol.55, pp.22-2844, 2002.

J. A. Baross and S. E. Hoffman, Submarine hydrothermal vents and associated gradient environments as sites for the origin and evolution of life, Origins of life and evolution of the biosphere, vol.15, p.327, 1985.

H. Bekker, H. Berendsen, E. Dijkstra, S. Achterop, R. Van-drunen et al., GROMACS: A parallel computer for molecular dynamics simulations, Conference proceedings-Physics Computing 92, 1992.

K. S. Bender, H. B. Yen, C. L. Hemme, Z. Yang, Z. He et al., Analysis of a ferric uptake regulator (Fur) mutant of Desulfovibrio vulgaris Hildenborough, In: Applied and environmental microbiology, vol.73, pp.5389-5400, 2007.

H. J. Berendsen, J. R. Grigera, and T. P. Straatsma, The missing term in effective pair potentials, The Journal of Physical Chemistry, vol.91, pp.6269-6271, 1987.

H. J. Berendsen, J. V. Postma, W. F. Van-gunsteren, A. Dinola, and J. Haak, Molecular dynamics with coupling to an external bath, The Journal of chemical physics, vol.81, pp.3684-3690, 1984.

S. Bereswill, . Lichte, . Vey, M. Fassbinder, and . Kist, Cloning and characterization of the fur gene from Helicobacter pylori, In: FEMS microbiology letters, vol.159, pp.378-1097, 1998.

M. B. Bickle, E. Dusserre, O. Moncorgé, H. Bottin, and P. Colas, Selection and characterization of large collections of peptide aptamers through optimized yeast two-hybrid procedures, In: Nature protocols, vol.1, pp.1750-2799, 2006.

R. W. Binsted, S. S. Strange, and . Hasnain, Constrained and restrained refinement in EXAFS data analysis with curved wave theory, Biochemistry 31, pp.6-2960, 1992.

J. H. Blum, S. L. Dove, J. J. Hochschild, and . Mekalanos, Isolation of peptide aptamers that inhibit intracellular processes, Proceedings of the National Academy of Sciences of the United States of America 97, pp.2241-2246, 2000.

C. Bonfio, E. Godino, M. Corsini, F. Fabrizi-de-biani, G. Guella et al., Prebiotic ironsulfur peptide catalysts generate a pH gradient across model membranes of late protocells, Nature Catalysis, vol.1, pp.616-623, 2018.

M. Born and R. Oppenheimer, Zur Quantentheorie der Molekeln, Annalen der Physik, vol.84, p.457, 1927.

E. S. Boyd, K. M. Thomas, Y. Dai, J. M. Boyd, and F. W. Outten, Interplay between oxygen and Fe-S cluster biogenesis: insights from the Suf pathway, Biochemistry 53, pp.5834-5847, 2014.

V. Braun, S. Schäffer, K. Hantke, and W. Tröger, Regulation of Gene Expression by Iron, The Molecular Basis of Bacterial Metabolism, pp.978-981, 1990.

P. Brescia and P. Banks, Multi-Volume Analysis of Nucleic Acids Using the Epoch? Spectrophotometer System, 2009.

B. R. Brooks, R. E. Bruccoleri, B. D. Olafson, D. J. States, S. Swaminathan et al., CHARMM: a program for macromolecular energy, minimization, and dynamics calculations, J. Comput. Chem, vol.4, pp.187-217, 1983.

A. Brunning, A Brief Guide to the Twenty Common Amino Acids, pp.2018-2027

A. Brunning, Different classes of antibiotics-An overview, pp.2018-2024

N. Bsat, . Herbig, P. Casillas-martinez, J. D. Setlow, and . Helmann, Bacillus subtilis contains multiple Fur homologues: identification of the iron uptake (Fur) and peroxide regulon (PerR) repressors, In: Molecular microbiology, vol.29, issue.1, pp.950-382, 1998.

O. Bun?u and Y. Joly, Self-consistent aspects of x-ray absorption calculations, In: Journal of physics. Condensed matter : an Institute of Physics journal, pp.1361-648, 2009.

J. Butcher, S. Sarvan, J. S. Brunzelle, J. Couture, and A. Stintzi, Structure and regulon of Campylobacter jejuni ferric uptake regulator Fur define apo-Fur regulation, Proceedings of the National Academy of Sciences of the United States of America, vol.109, pp.10047-10052, 2012.

S. B. Calderwood and J. J. Mekalanos, Iron regulation of Shiga-like toxin expression in Escherichia coli is mediated by the fur locus, In: Journal of bacteriology, vol.169, pp.21-9193, 1987.

J. Castresana, Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis, In: Molecular biology and evolution, vol.17, pp.737-4038, 2000.

C. Chieh and . Chieh, , pp.2018-2027, 2018.

D. Chirgadze, Protein Crystallisation in Action, 2001.

C. Cissé, S. V. Mathieu, M. B. Abeih, L. Flanagan, S. Vitale et al., Inhibition of the ferric uptake regulator by peptides derived from anti-FUR peptide aptamers: coupled theoretical and experimental approaches, ACS chemical biology, vol.9, pp.1554-8937, 2014.

P. Colas, . Cohen, . Jessen, . Grishina, R. Mccoy et al., Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2, In: Nature, vol.380, pp.548-550, 1996.

J. Collet and J. Messens, Structure, function, and mechanism of thioredoxin proteins, Antioxidants & redox signaling, pp.1557-7716, 2010.

R. Constanciel and R. Contreras, Self consistent field theory of solvent effects representation by continuum models: Introduction of desolvation contribution, Theoretica chimica acta, vol.65, pp.1-11, 1984.

W. Cornell, P. Cieplak, C. Bayly, I. Gould, K. Merz et al., A second generation force field for the simulation of proteins and nucleic acids, J. Am. Chem. Soc, vol.117, pp.5179-5197, 1995.

M. Coy, . Doyle, J. B. Besser, and . Neilands, Site-directed mutagenesis of the ferric uptake regulation gene of Escherichia coli, Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, pp.966-0844, 1994.

S. Crouzy, T. Woolf, and B. Roux, A molecular dynamics study of gating in dioxolane-linked gramicidin A channels, In: Biophys. J, vol.67, pp.1370-1386, 1994.

M. , Polarity and permeation profiles in lipid membranes, Proc. Natl. Acad. Sci. U. S. A, vol.98, pp.7777-7782, 2001.

T. Darden, D. York, and L. Pedersen, Particle mesh Ewald: An Nlog(N) method for Ewald sums in large systems, The Journal of Chemical Physics, vol.98, pp.10089-10092, 1993.

N. Datta and V. M. Hughes, Plasmids of the same Inc groups in Enterobacteria before and after the medical use of antibiotics, Nature, vol.306, pp.28-0836, 1983.

B. D'autreaux, D. Touati, B. Bersch, J. Latour, and I. Michaud-soret, Direct inhibition by nitric oxide of the transcriptional ferric uptake regulation protein via nitrosylation of the iron, Proceedings of the National Academy of Sciences of the United States of America, pp.16619-16624, 2002.

B. D'autréaux, L. Pecqueur, A. Gonzalez-de-peredo, R. E. Diederix, C. Caux-thang et al., Reversible redox-and zinc-dependent dimerization of the Escherichia coli fur protein, In: Biochemistry, vol.46, pp.1329-1342, 2007.

L. A. David and E. J. Alm, Rapid evolutionary innovation during an Archaean genetic expansion, In: Nature, vol.469, pp.1476-4687, 2011.

J. Davies, Inactivation of antibiotics and the dissemination of resistance genes, In: Science, pp.36-8075, 1994.

J. Davies, Specialized microbial metabolites: functions and origins, In: The Journal of antibiotics, vol.66, issue.7, pp.361-364, 2013.

J. Davies and D. Davies, Origins and evolution of antibiotic resistance, In: Microbiology and molecular biology reviews : MMBR, vol.74, pp.1098-5557, 2010.

/. Mmbr, , pp.16-26

V. M. Costa, C. E. King, L. Kalan, M. Morar, W. W. Sung et al., Antibiotic resistance is ancient, In: Nature, vol.477, pp.1476-4687, 2011.

. V-de-lorenzo, . Herrero, J. B. Giovannini, and . Neilands, Fur (ferric uptake regulation) protein and CAP (catabolite-activator protein) modulate transcription of fur gene in Escherichia coli, European journal of biochemistry, vol.173, pp.14-2956, 1988.

I. Delany, G. Spohn, R. Rappuoli, and V. Scarlato, An anti-repression Fur operator upstream of the promoter is required for iron-mediated transcriptional autoregulation in Helicobacter pylori, In: Molecular microbiology, vol.50, pp.950-382, 2003.

I. Delany, R. Rappuoli, and V. Scarlato, Fur functions as an activator and as a repressor of putative virulence genes in Neisseria meningitidis, In: Molecular microbiology, vol.52, 2004.

I. Delany, R. Ieva, A. Soragni, M. Hilleringmann, R. Rappuoli et al., In vitro analysis of protein-operator interactions of the NikR and fur metal-responsive regulators of coregulated genes in Helicobacter pylori, In: Journal of bacteriology, vol.187, pp.21-9193, 2005.

I. Delany, R. Grifantini, E. Bartolini, R. Rappuoli, and V. Scarlato, Effect of Neisseria meningitidis fur mutations on global control of gene transcription, In: Journal of bacteriology, vol.188, issue.7

, , pp.2483-2492, 2006.

Z. Deng, Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator, Nature communications, vol.6, pp.2041-1723, 2015.

C. Dian, S. Vitale, G. A. Leonard, C. Bahlawane, C. Fauquant et al., The structure of the Helicobacter pylori ferric uptake regulator Fur reveals three functional metal binding sites, In: Molecular microbiology, pp.1365-2958, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00936385

A. C. Dlouhy and C. E. Outten, The iron metallome in eukaryotic organisms, In: Metal ions in life sciences, vol.12, pp.1559-0836, 2013.

T. Dobzhansky, Nothing in Biology Makes Sense except in the Light of Evolution, The American Biology Teacher, vol.35, p.27685, 1973.

C. L. Dupont, A. Butcher, R. E. Valas, P. E. Bourne, and G. Caetano-anollés, History of biological metal utilization inferred through phylogenomic analysis of protein structures, Proceedings of the National Academy of Sciences of the United States of America, vol.107, pp.10567-10572, 2010.

B. Efron, Bootstrap Methods: Another Look at the Jackknife", vol.7, pp.1-26, 1979.

D. Eisenberg and L. Wesson, Atomic solvation parameters applied to molecular dynamics of proteins in solution, In: Protein Sci, vol.1, p.227235, 1992.

G. L. Ellman, Tissue sulfhydryl groups, Archives of biochemistry and biophysics, vol.82, pp.3-9861, 1959.

P. Emsley, B. Lohkamp, W. G. Scott, and K. Cowtan, Features and Development of Coot, Acta Crystallographica Section D-Biological Crystallography, vol.66, pp.486-501, 2010.

F. D. Ernst, S. Bereswill, B. Waidner, J. Stoof, U. Mäder et al., Transcriptional profiling of Helicobacter pylori Furand iron-regulated gene expression, In: Microbiology (Reading, England), pp.533-546, 2005.

J. F. Ernst, R. L. Bennett, and L. I. Rothfield, Constitutive expression of the iron-enterochelin and ferrichrome uptake systems in a mutant strain of Salmonella typhimurium, In: Journal of bacteriology, vol.135, pp.21-9193, 1978.

L. Escolar, . Pérez-martín, and . Lorenzo, Binding of the fur (ferric uptake regulator) repressor of Escherichia coli to arrays of the GATAAT sequence, In: Journal of molecular biology, vol.283, pp.22-2836, 1998.

L. Escolar, . Pérez-martín, and . Lorenzo, Opening the iron box: transcriptional metalloregulation by the Fur protein, In: Journal of bacteriology, vol.181, pp.21-9193, 1999.

L. Escolar, . Pérez-martín, and . Lorenzo, Evidence of an unusually long operator for the fur repressor in the aerobactin promoter of Escherichia coli, In: The Journal of biological chemistry, pp.24709-24714, 2000.

U. Essmann, M. Perera, . Berkowitz, H. Darden, L. Lee et al., A smooth particle mesh Ewald method, Journal of Chemical Physics, vol.103, pp.8577-8593, 1995.

P. P. Ewald, Die Berechnung optischer und elektrostatischer Gitterpotentiale, Annalen der Physik, vol.369, pp.253-287, 1921.

,

B. Falkowski and S. , Biogeochemical Controls and Feedbacks on Ocean Primary Production, Science, vol.281, pp.1095-9203, 1998.

J. Felsenstein, CONFIDENCE LIMITS ON PHYLOGENIES: AN APPROACH USING THE BOOTSTRAP, In: Evolution; international journal of organic evolution, vol.39, pp.1558-5646, 1985.

P. Ferrara, J. Apostolakis, and A. Caflisch, Evaluation of a fast implicit solvent model for molecular dynamics simulations, In: Proteins, vol.46, pp.24-33, 2002.

A. M. Ferrenberg and R. H. Swendsen, Optimized Monte Carlo data analysis, Phys. Rev. Lett, vol.63, pp.1195-1198, 1989.

S. Fields and . Song, A novel genetic system to detect protein-protein interactions, Nature, vol.340, pp.28-0836, 1989.

M. F. Fillat, The FUR (ferric uptake regulator) superfamily: diversity and versatility of key transcriptional regulators, Archives of biochemistry and biophysics, vol.546, pp.1096-0384, 2014.

M. V. Franke, P. V. Petoukhov, . Konarev, . Panjkovich, H. D. Tuukkanen et al., ATSAS 2.8 : a comprehensive data analysis suite for small-angle scattering from macromolecular solutions, In: Journal of applied crystallography, vol.50, pp.1212-1225, 2017.

M. Fuangthong, A. F. Herbig, N. Bsat, and J. D. Helmann, Regulation of the Bacillus subtilis fur and perR genes by PerR: not all members of the PerR regulon are peroxide inducible, In: Journal of bacteriology, vol.184, pp.21-9193, 2002.

H. Gancz, S. Censini, and D. S. Merrell, Iron and pH homeostasis intersect at the level of Fur regulation in the gastric pathogen Helicobacter pylori, In: Infection and immunity, vol.74, pp.19-9567, 2006.

H. Gao, D. Zhou, Y. Li, Z. Guo, Y. Han et al., The iron-responsive Fur regulon in Yersinia pestis, In: Journal of bacteriology, vol.190, issue.8

, , pp.3063-3075, 2008.

J. A. Garibaldi and J. B. Neilands, Formation of iron-binding compounds by micro-organisms, In: Nature, vol.177, pp.28-0836, 1956.

V. Gasser, L. Guillon, O. Cunrath, and I. J. Schalk, Cellular organization of siderophore biosynthesis in Pseudomonas aeruginosa: Evidence for siderosomes, In: Journal of inorganic biochemistry, vol.148, pp.1873-3344, 2015.

B. A. Gilston, S. Wang, M. D. Marcus, M. A. Canalizo-hernández, E. P. Swindell et al., Structural and Mechanistic Basis of Zinc Regulation Across the E. coli Zur Regulon, PLOS Biology, vol.12, pp.1-16, 2014.

K. O. Glatter and O. , Data treatment, p.16012436, 1982.

M. Gouy, S. Guindon, and O. Gascuel, SeaView version 4: A multiplatform graphical user interface for sequence alignment and phylogenetic tree building, Molecular biology and evolution, pp.1537-1719, 2010.
URL : https://hal.archives-ouvertes.fr/lirmm-00511794

L. Greengard and V. Rokhlin, A Fast Algorithm For Particle Simulations, J. Comput. Chem, vol.73, p.325, 1987.

S. Guindon, J. Dufayard, V. Lefort, M. Anisimova, W. Hordijk et al., New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0, In: Systematic biology, vol.59, issue.3, pp.307-321, 2010.
URL : https://hal.archives-ouvertes.fr/lirmm-00511784

A. Guinier, La diffraction des rayons X aux très petits angles : application à l'étude de phénomènes ultramicroscopiques, Ann. Phys, vol.11, pp.161-237, 1939.

T. Halgren, Representation of van der Waals (vdW) Interactions in Molecular Mechanics Force Fields: Potential Form, Combination Rules, and vdW Parameters, Journal of the American Chemical Society, vol.114, p.7827, 1992.

A. Hamdi and P. Colas, Yeast two-hybrid methods and their applications in drug discovery, Trends in pharmacological sciences, vol.33, pp.1873-3735, 2012.

K. Hantke, Regulation of ferric iron transport in Escherichia coli K12: isolation of a constitutive mutant, In: Molecular & general genetics : MGG, vol.182, pp.26-8925, 1981.

K. Hantke, Cloning of the repressor protein gene of iron-regulated systems in Escherichia coli K12, Molecular & general genetics : MGG 197, pp.26-8925, 1984.

K. Hantke, Iron and metal regulation in bacteria, In: Current opinion in microbiology, vol.4, pp.1369-5274, 2001.

K. Hantke, Selection procedure for deregulated iron transport mutants (fur) in Escherichia coli K 12: fur not only affects iron metabolism, Molecular and General Genetics MGG, vol.210, p.135, 1987.

D. M. Hillis and J. J. Bull, An Empirical Test of Bootstrapping as a Method for Assessing Confidence in Phylogenetic Analysis, Systematic Biology, vol.42, pp.182-192, 1993.

H. D. Holland, M. Lazar, and . Mccaffrey, Evolution of the atmosphere and oceans, In: Nature, vol.320, pp.27-33, 1986.

L. Holm, H. Sander, . Rüterjans, . Schnarr, . Fogh et al., LexA repressor and iron uptake regulator from Escherichia coli: new members of the CAP-like DNA binding domain superfamily, In: Protein engineering, vol.7, pp.269-2139, 1994.

A. H. Holmes, L. S. Moore, A. Sundsfjord, M. Steinbakk, S. Regmi et al., Understanding the mechanisms and drivers of antimicrobial resistance, Lancet, pp.176-187, 2016.

K. Holmes, F. Mulholland, B. M. Pearson, C. Pin, J. Mcnicholl-kennedy et al., Campylobacter jejuni gene expression in response to iron limitation and the role of Fur, In: Microbiology (Reading, England), pp.243-257, 2005.

G. Hoover, Canonical dynamics: Equilibrium phase-space distributions, Phys. Rev. A, vol.31, p.1695, 1985.

M. J. Horsburgh, S. J. Ingham, and . Foster, In Staphylococcus aureus, fur is an interactive regulator with PerR, contributes to virulence, and Is necessary for oxidative stress resistance through positive regulation of catalase and iron homeostasis, In: Journal of bacteriology, vol.183, issue.2

, , pp.468-475, 2001.

K. Hsin, Y. Sheng, M. M. Harding, P. Taylor, and M. D. Walkinshaw, MESPEUS: a database of the geometry of metal sites in proteins, Journal of Applied Crystallography, vol.41, pp.963-968, 2008.

J. S. Hub, B. L. De-groot, D. Van-der, and . Spoel, g_wham: A Free Weighted Histogram Analysis Implementation Including Robust Error and Autocorrelation Estimates, Journal of Chemical Theory and Computation, vol.6, pp.3713-3720, 2010.

,

W. Humphrey, A. Dalke, and K. Schulten, VMD: visual molecular dynamics, Journal of molecular graphics, vol.14, pp.33-38, 1996.

C. Huygens, Traité de la lumière. chez Pierre Vander Aa marchand libraire, p.1690

H. Irving and R. J. Williams, Order of Stability of Metal Complexes, Nature, vol.162, p.746, 1948.

. Iupac, Periodic Table of elements, pp.2018-2027

L. Jacquamet, . Aberdam, J. L. Adrait, J. M. Hazemann, . Latour et al., Xray absorption spectroscopy of a new zinc site in the fur protein from Escherichia coli, In: Biochemistry, vol.37, pp.2564-2571, 1998.
URL : https://hal.archives-ouvertes.fr/hal-01062966

B. H. Jans and . Hanssen, Docking redone, pp.2018-2027

W. Jorgensen and J. Tirado-rives, The OPLS Potential Functions for Proteins. Energy Minimization for Crystal of Cyclic Peptides and Crambin, J. Am. Chem. Soc, vol.110, pp.1657-1666, 1988.

G. F. Joyce, RNA evolution and the origins of life, In: Nature, vol.338, pp.28-0836, 1989.

W. Kabsch, XDS, Acta crystallographica. Section D, Biological crystallography, vol.66, pp.1399-1446, 2010.

E. Krissinel and K. Henrick, Inference of Macromolecular Assemblies from Crystalline State, Journal of Molecular Biology, vol.372, pp.22-2836, 2007.

S. Kumar, D. Bouzida, R. Swendsen, P. Kollman, and J. Rosenberg, The Weighted Histogram Analysis Method for free-energy calculations on biomolecules. I. The method, J. Comput. Chem, vol.13, pp.1011-1021, 1992.

M. Kurcinski, M. Jamroz, M. Blaszczyk, A. Kolinski, and S. Kmiecik, CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site, Nucleic acids research, vol.43, 2015.

M. Kuroda, Whole genome sequencing of meticillin-resistant Staphylococcus aureus, Lancet, pp.140-6736, 2001.

J. L. Lavrrar, C. A. Christoffersen, and M. A. Mcintosh, Fur-DNA interactions at the bidirectional fepDGC-entS promoter region in Escherichia coli, In: Journal of molecular biology, vol.322, issue.5

T. Lazaridis and M. Karplus, Effective energy function for proteins in solution, Proteins, vol.35, pp.133-152, 1999.

A. Leach, Molecular Modelling, 2001.

H. Lee, L. Heo, M. S. Lee, and C. Seok, GalaxyPepDock: a protein-peptide docking tool based on interaction similarity and energy optimization, In: Nucleic acids research, vol.43, 2015.

H. Lee, K. Park, A. Y. Lee, S. G. Park, B. C. Park et al., Regulation of fur expression by RpoS and fur in Vibrio vulnificus, In: Journal of bacteriology, vol.185, pp.21-9193, 2003.

J. W. Little, D. W. Mount, and C. R. Yanisch-perron, Purified lexA protein is a repressor of the recA and lexA genes, Proceedings of the National Academy of Sciences of the United States of America, vol.78, pp.27-8424, 1981.

C. M. Litwin and S. B. Calderwood, Analysis of the complexity of gene regulation by fur in Vibrio cholerae, In: Journal of bacteriology, vol.176, pp.21-9193, 1994.

N. London, B. Raveh, E. Cohen, G. Fathi, and O. Schueler-furman, Rosetta FlexPepDock web server-high resolution modeling of peptide-protein interactions, In: Nucleic acids research, vol.39, 2011.

. V-de-lorenzo, . Wee, J. B. Herrero, and . Neilands, Operator sequences of the aerobactin operon of plasmid ColV-K30 binding the ferric uptake regulation (fur) repressor, In: Journal of bacteriology, vol.169, issue.6, pp.21-9193, 1987.

. V-de-lorenzo, . Giovannini, J. B. Herrero, and . Neilands, Metal ion regulation of gene expression. Fur repressor-operator interaction at the promoter region of the aerobactin system of pColV-K30, In: Journal of molecular biology, vol.203, pp.22-2836, 1988.

D. M. and F. , Skript zur Mathematik fuer die Molekulare Biotechnologie, vol.3, 2003.

. Mackerell, Internal coordinates for bonded interactons, pp.2018-2027

J. L. Martinez, The role of natural environments in the evolution of resistance traits in pathogenic bacteria, In: Proceedings. Biological sciences, vol.276, 1667.

J. L. Martinez, M. B. Sánchez, L. Martínez-solano, A. Hernandez, L. Garmendia et al., Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems, In: FEMS microbiology reviews, vol.33, pp.1574-6976, 2009.

E. Massé and S. Gottesman, A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli, Proceedings of the National Academy of Sciences of the United States of America, pp.4620-4625, 2002.

E. Massé, C. K. Vanderpool, and S. Gottesman, Effect of RyhB small RNA on global iron use in Escherichia coli, In: Journal of bacteriology, vol.187, pp.21-9193, 2005.

S. Mathieu, C. Cissé, S. Vitale, A. Ahmadova, M. Degardin et al., From Peptide Aptamers to Inhibitors of FUR, Bacterial Transcriptional Regulator of Iron Homeostasis and Virulence, ACS chemical biology, vol.11, pp.2519-2528, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02008298

P. Mazodier and . Davies, Gene transfer between distantly related bacteria, In: Annual review of genetics, vol.25, pp.147-171, 1991.

G. W. Mccoy and C. W. Chapin, Further Observations on a Plague-Like Disease of Rodents with a Preliminary Note on the Causative Agent, Bacterium tularense, The Journal of Infectious Diseases, vol.10, pp.61-72, 1912.

J. P. Mchugh, F. Rodríguez-quinoñes, H. Abdul-tehrani, D. A. Svistunenko, R. K. Poole et al.,

S. C. Cooper and . Andrews, Global iron-dependent gene regulation in Escherichia coli. A new mechanism for iron homeostasis, In: The Journal of biological chemistry, pp.29478-29486, 2003.

D. Mcquaerrie, Statistical Mechanics, University Science Books Sansalito, 2000.

E. Merritt, X-ray Anomalous Scattering, pp.2018-2025

A. R. Mey, E. E. Wyckoff, V. Kanukurthy, C. R. Fisher, and S. M. Payne, Iron and fur regulation in Vibrio cholerae and the role of fur in virulence, In: Infection and immunity, vol.73, pp.19-9567, 2005.

I. Michaud-soret, . Adrait, . Jaquinod, . Forest, J. M. Touati et al., Electrospray ionization mass spectrometry analysis of the apo-and metal-substituted forms of the Fur protein, In: FEBS letters, vol.413, pp.14-5793, 1997.
URL : https://hal.archives-ouvertes.fr/hal-01062972

S. A. Mills and M. A. Marletta, Metal binding characteristics and role of iron oxidation in the ferric uptake regulator from Escherichia coli, Biochemistry 44, pp.13553-13559, 2005.

M. L. Of, Molecular Biology. SCOP2, pp.2018-2028

G. M. Morris, D. S. Goodsell, R. S. Halliday, R. Huey, W. E. Hart et al., Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function, Journal of Computational Chemistry, vol.19, pp.1639-1662, 1998.

,

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.

J. M. Munita and C. A. Arias, Mechanisms of Antibiotic Resistance, In: Microbiology spectrum, vol.4, 2016.

M. Newville, Fundamentals of XAFS, 2004.

E. Van-nood, A. Vrieze, M. Nieuwdorp, S. Fuentes, E. G. Zoetendal et al., Duodenal infusion of donor feces for recurrent Clostridium difficile, In: The New England journal of medicine, vol.368, pp.1533-4406, 2013.

S. Nose, A unified formulation of the constant temperature molecular-dynamics methods, J. Chem. Phys, vol.81, p.511, 1984.

C. D. Okafor, K. A. Lanier, A. S. Petrov, S. S. Athavale, J. C. Bowman et al., Iron mediates catalysis of nucleic acid processing enzymes: support for Fe(II) as a cofactor before the great oxidation event, In: Nucleic acids research, vol.45, pp.3634-3642, 2017.

A. Onufriev, D. Bashford, and D. Case, Effective Born radii in the generalized Born approximation: The importance of being perfect, J Comp Chem, vol.23, pp.1297-1304, 2002.

C. Oostenbrink, A. Villa, A. E. Mark, and W. F. Van-gunsteren, A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6, J Comput Chem, vol.25, pp.1656-1676, 2004.

J. O'neill, Tackling drug-resistant infections globally: final report and recommendations, The Review On Antimicrobial Resistance, 2016.

L. Pallecchi, C. Lucchetti, A. Bartoloni, F. Bartalesi, A. Mantella et al., Population structure and resistance genes in antibiotic-resistant bacteria from a remote community with minimal antibiotic exposure, Antimicrobial agents and chemotherapy, vol.51, pp.1179-1184, 2007.

L. D. Palmer and E. P. Skaar, Transition Metals and Virulence in Bacteria, In: Annual review of genetics, vol.50, pp.1545-2948, 2016.

M. Parrinello and A. Rahman, Polymorphic transitions in single crystals: A new molecular dynamics method, Journal of Applied Physics, vol.52, pp.7182-7190, 1981.

G. Patey and J. Valleau, A Monte Carlo method for obtaining the interionic potential of mean force in ionic solution, J. Chem. Phys, vol.63, pp.2334-2339, 1975.

L. Pecqueur, B. D'autréaux, J. Dupuy, Y. Nicolet, L. Jacquamet et al., Structural changes of Escherichia coli ferric uptake regulator during metaldependent dimerization and activation explored by NMR and X-ray crystallography, In: The Journal of biological chemistry, vol.281, pp.21286-21295, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00381824

J. Pérard and S. Ollagnier-de-choudens, Iron-sulfur clusters biogenesis by the SUF machinery: close to the molecular mechanism understanding, JBIC Journal of Biological Inorganic Chemistry, vol.23, pp.1432-1327, 2018.

A. Gonzalez-de-peredo, J. M. Saint-pierre, . Latour, E. Michaud-soret, and . Forest, Conformational changes of the ferric uptake regulation protein upon metal activation and DNA binding; first evidence of structural homologies with the diphtheria toxin repressor, In: Journal of molecular biology, vol.310, issue.1, pp.22-2836, 2001.
URL : https://hal.archives-ouvertes.fr/hal-01062957

O. Q. Pich, B. M. Carpenter, J. J. Gilbreath, and D. S. Merrell, Detailed analysis of Helicobacter pylori Fur-regulated promoters reveals a Fur box core sequence and novel Fur-regulated genes, In: Molecular microbiology, vol.84, issue.5, pp.1365-2958, 2012.

E. Pohl, J. C. Haller, A. Mijovilovich, W. Meyer-klaucke, E. Garman et al., Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator, In: Molecular microbiology, vol.47, pp.950-382, 2003.

G. Porod, Die Röntgenkleinwinkelstreuung von dichtgepackten kolloiden Systemen, KolloidZeitschrift, vol.124, pp.1435-1536, 1951.

/. Doi,

C. W. Price, W. A. Randall, V. L. Chandler, and R. J. Reedy, Observations on the in Vivo and in Vitro Development of Bacterial Resistance to Streptomycin, In: Journal of bacteriology, vol.53, issue.4

R. W. Prince, C. D. Cox, and M. L. Vasil, Coordinate regulation of siderophore and exotoxin A production: molecular cloning and sequencing of the Pseudomonas aeruginosa fur gene, In: Journal of bacteriology, vol.175, pp.21-9193, 1993.

O. Proux, V. Nassif, A. Prat, O. Ulrich, E. Lahera et al., Feedback system of a liquid-nitrogen-cooled double-crystal monochromator: design and performances, In: Journal of synchrotron radiation, vol.13, pp.59-68, 2006.
URL : https://hal.archives-ouvertes.fr/insu-00713235

K. Prévost, H. Salvail, G. Desnoyers, J. Jacques, E. Phaneuf et al., The small RNA RyhB activates the translation of shiA mRNA encoding a permease of shikimate, a compound involved in siderophore synthesis, In: Molecular microbiology, vol.64, issue.5, pp.1260-1273, 2007.

C. D. Putnam, M. Hammel, G. L. Hura, and J. A. Tainer, X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution, In: Quarterly reviews of biophysics, vol.40, pp.191-285, 2007.

J. Pérard, S. Nader, M. Levert, L. Arnaud, P. Carpentier et al., Structural and functional studies of the metalloregulator Fur identify a promoter-binding mechanism and its role in Francisella tularensis virulence, Communications Biology, vol.1, issue.1, pp.2399-3642, 2018.

J. Pérard, J. Covès, M. Castellan, C. Solard, M. Savard et al., Quaternary Structure of Fur Proteins, a New Subfamily of Tetrameric Proteins, In: Biochemistry, vol.55, pp.1503-1515, 2016.

. R-core-team, R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, 2013.

B. Ravel and . Newville, ARTEMIS, HEPHAESTUS: data analysis for X-ray absorption spectroscopy using IFEFFIT, In: Journal of synchrotron radiation, vol.12, pp.537-541, 2005.

R. B. Rea, C. G. Gahan, and C. Hill, Disruption of Putative Regulatory Loci in Listeria monocytogenes Demonstrates a Significant Role for Fur and PerR in Virulence, Infection and Immunity, vol.72, pp.717-727, 2004.

J. J. Rehr, J. J. Kas, F. D. Vila, M. P. Prange, and K. Jorissen, Parameter-free calculations of X-ray spectra with FEFF9, In: Physical chemistry chemical physics : PCCP, vol.12, issue.21, pp.1463-9084, 2010.

H. Research, Hanging Drop Vapor Diffusion Crystallization, 2017.

H. Research, Sitting Drop Vapor Diffusion Crystallization, 2017.

, Central Asian and Eastern European Surveillance of Antimicrobial Resistance, Annual report, 2016.

, Central Asian and Eastern European Surveillance of Antimicrobial Resistance, Annual report, 2017.

, Global action plan on Antimicrobial Resistance, WHO Library Cataloguing-in-Publication Data, 2015.

, Global Antimicrobial Resistance Surveillance System (GLASS) Report, 2015.

F. Richards, Areas, volumes, packing, and protein structure, Ann. Rev. Biophys. Bioeng, vol.6, pp.151-176, 1977.

R. Rohs, X. Jin, S. M. West, R. Joshi, B. Honig et al., Origins of specificity in proteinDNA recognition, In: Annual review of biochemistry, vol.79, pp.1545-4509, 2010.

B. Roux and T. Simonson, Implicit Solvent Models, Biophys. Chem, vol.78, pp.1-20, 1999.

D. M. Ruden, Y. Ma, . Li, M. Wood, and . Ptashne, Generating yeast transcriptional activators containing no yeast protein sequences, Nature, vol.350, pp.250-252, 1991.

M. J. Russell, R. M. Daniel, A. J. Hall, and J. A. Sherringham, A hydrothermally precipitated catalytic iron sulphide membrane as a first step toward life, Journal of Molecular Evolution, vol.39, pp.231-243, 1994.

M. R. Saito, R. J. Wormald, and . Williams, Some structural features of the iron-uptake regulation protein, European journal of biochemistry, vol.197, pp.14-2956, 1991.

S. Sarvan, F. Charih, M. Askoura, J. Butcher, J. S. Brunzelle et al., Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators, In: Scientific reports, vol.8, issue.1, pp.2045-2322, 2018.

I. J. Schalk, Innovation and originality in the strategies developed by bacteria to get access to iron, Chembiochem : a European journal of chemical biology, vol.14, pp.1439-7633, 2013.

I. J. Schalk and L. Guillon, Pyoverdine biosynthesis and secretion in Pseudomonas aeruginosa: implications for metal homeostasis, In: Environmental microbiology, vol.15, issue.6, pp.1661-1673, 2013.

N. Schmid, A. P. Eichenberger, A. Choutko, S. Riniker, M. Winger et al., Definition and testing of the GROMOS force-field versions 54A7 and 54B7, European Biophysics Journal, vol.40, p.843, 2011.

S. Schäffer, V. Hantke, and . Braun, Nucleotide sequence of the iron regulatory gene fur, In: Molecular & general genetics : MGG, vol.200, pp.26-8925, 1985.

M. A. Sheikh and G. L. Taylor, Crystal structure of the Vibrio cholerae ferric uptake regulator (Fur) reveals insights into metal co-ordination, In: Molecular microbiology, vol.72, issue.5, pp.1365-2958, 2009.

M. R. Shirts, D. L. Mobley, J. D. Chodera, and V. S. Pande, Accurate and Efficient Corrections for Missing Dispersion Interactions in Molecular Simulations, The Journal of Physical Chemistry B, vol.111, pp.13052-13063, 2007.

F. Sievers, A. Wilm, D. Dineen, T. J. Gibson, K. Karplus et al., Fast, scalable generation of highquality protein multiple sequence alignments using Clustal Omega, In: Molecular systems biology, vol.7, pp.1744-4292, 2011.

E. P. Skaar, The battle for iron between bacterial pathogens and their vertebrate hosts, In: PLoS pathogens, vol.6, 2010.

T. M. Staggs and R. D. Perry, Identification and cloning of a fur regulatory gene in Yersinia pestis, In: Journal of bacteriology, vol.173, pp.21-9193, 1991.

P. S. Stewart and J. W. Costerton, Antibiotic resistance of bacteria in biofilms, In: Lancet, pp.140-6736, 2001.

W. Still, A. Tempczyk, R. Hawley, and T. Hendrickson, Semianalytical treatment of solvation for molecular mechanics and dynamics, J. Am. Chem. Soc, vol.112, pp.6127-6129, 1990.

I. Stojiljkovic and . Hantke, Functional domains of the Escherichia coli ferric uptake regulator protein (Fur), Molecular & general genetics : MGG 247, pp.26-8925, 1995.

R. Stote and D. States, On the Treatment of Electrostatic Interactions in Biomolecular Simulation, Journal de Chimie Physique, vol.88, p.2419, 1991.

R. W. Strange, N. J. Blackburn, P. F. Knowles, and S. S. Hasnain, X-ray absorption spectroscopy of metal-histidine coordination in metalloproteins. Exact simulation of the EXAFS of tetrabis(imidazole)copper(II) nitrate and other copper-imidazole complexes by the use of a multiple-scattering treatment, Journal of the American Chemical Society, vol.109, pp.7157-7162, 1987.

H. J. Strutt, On the scattering of light by small particles, The London, vol.41, pp.447-454, 1871.

D. I. Svergun and M. H. Koch, Small-angle scattering studies of biological macromolecules in solution, In: Reports on Progress in Physics, vol.66, pp.1735-1782, 2003.

A. Theisen, Refractive increment data-book for polymer and biomolecular scientists, vol.isbn, pp.1-897676, 2000.

B. M. Tissue, , pp.2018-2027, 2018.

V. J. Torres, A. S. Attia, W. J. Mason, M. I. Hood, B. D. Corbin et al., Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia, In: Infection and immunity, vol.78, pp.1618-1628, 2010.

G. M. Torrie and J. P. Valleau, Monte Carlo free energy estimates using non-Boltzmann sampling: application to the sub-critical Lennard-Jones fluid, Chem. Phys. Let, vol.28, 1974.

D. Touati, . Jacques, . Tardat, S. Bouchard, and . Despied, Lethal oxidative damage and mutagenesis are generated by iron in delta fur mutants of Escherichia coli: protective role of superoxide dismutase, In: Journal of bacteriology, vol.177, pp.21-9193, 1995.

O. Trott and A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, In: Journal of computational chemistry, pp.455-461, 2010.

B. Troxell, M. L. Sikes, R. C. Fink, A. Vazquez-torres, J. Jones-carson et al., Fur negatively regulates hns and is required for the expression of HilA and virulence in Salmonella enterica serovar Typhimurium, In: Journal of bacteriology, vol.193, pp.497-505, 2011.

A. D. Tsaousis, E. Gentekaki, L. Eme, D. Gaston, and A. J. Roger, Evolution of the cytosolic iron-sulfur cluster assembly machinery in Blastocystis species and other microbial eukaryotes, Eukaryotic cell, vol.13, pp.1535-9786, 2014.

L. Valen, Molecular evolution as predicted by natural selection, In: Journal of Molecular Evolution, vol.3, issue.2, pp.1432-1432, 1974.

D. Van-der, E. Spoel, B. Lindahl, G. Hess, A. E. Groenhof et al., GROMACS: fast, flexible, and free, J Comput Chem, vol.26, pp.1701-1718, 2005.

L. Verlet, Computer "experiments" on classical fluids. I. Thermodynamical properties of LennardJones molecules, Phys. Rev, vol.159, issue.1, pp.98-103, 1967.

G. Veronesi, Advanced applications of X-ray absorption spectroscopy to the study of protein metal sites, 2010.

S. Vitale and ;. , Inhibiteurs anti-Fur et caractérisation de Fur d'Helicobacter pylori, 2009.

S. Vitale, C. Fauquant, D. Lascoux, K. Schauer, C. Saint-pierre et al., A ZnS(4) structural zinc site in the Helicobacter pylori ferric uptake regulator, In: Biochemistry, vol.48, issue.24, pp.5582-5591, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00936388

G. Wächtershäuser, Pyrite formation, the first energy source for life: a hypothesis, Systematic and Applied Microbiology, vol.10, pp.207-210, 1988.

K. J. Waldron and N. J. Robinson, How do bacterial cells ensure that metalloproteins get the correct metal?, In: Nature reviews. Microbiology, vol.7, pp.1740-1534, 2009.

K. J. Waldron, J. C. Rutherford, D. Ford, and N. J. Robinson, Metalloproteins and metal sensing, In: Nature, vol.460, pp.1476-4687, 2009.

F. Wang, S. Cheng, K. Sun, and L. Sun, Molecular analysis of the fur (ferric uptake regulator) gene of a pathogenic Edwardsiella tarda strain, In: Journal of microbiology, vol.46, issue.3, pp.1225-8873, 2008.

P. I. Watnick, H. Eto, S. B. Takahashi, and . Calderwood, Purification of Vibrio cholerae fur and estimation of its intracellular abundance by antibody sandwich enzyme-linked immunosorbent assay, In: Journal of bacteriology, vol.179, pp.21-9193, 1997.

E. M. Wellington, A. B. Boxall, P. Cross, E. J. Feil, W. H. Gaze et al., The role of the natural environment in the emergence of antibiotic resistance in gram-negative bacteria, The Lancet. Infectious diseases, pp.70317-70318, 2013.

P. J. Wilderman, N. A. Sowa, D. J. Fitzgerald, P. C. Fitzgerald, S. Gottesman et al., Identification of tandem duplicate regulatory small RNAs in Pseudomonas aeruginosa involved in iron homeostasis, Proceedings of the National Academy of Sciences of the United States of America, vol.101, issue.26, pp.9792-9797, 2004.

R. J. Williams, Iron in evolution, In: FEBS letters, vol.586, pp.479-484, 2012.

R. J. Williams, J. J. Fraústo-da, and . Silva, Evolution was chemically constrained, In: Journal of theoretical biology, vol.220, pp.22-5193, 2003.

C. R. Woese, M. L. Kandler, and . Wheelis, Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya, Proceedings of the National Academy of Sciences of the United States of America, vol.87, pp.27-8424, 1990.

P. J. Wyatt, Light scattering and the absolute characterization of macromolecules, Analytica Chimica Acta, vol.272, pp.1-40, 1993.

E. E. Zheleznova, J. H. Crosa, and R. G. Brennan, Characterization of the DNA-and metalbinding properties of Vibrio anguillarum Fur reveals conservation of a structural Zn2+ ion, Journal of bacteriology, vol.182, pp.6264-6267, 2000.

, EcFur-140 is a good tool to study EcFur-WT inhibition

, Acknowledgements LabEx ARCANE

?. Biocat-team:-?-christine-cavazza-?-philippe-carpentier-?-julien-pérard and I. Pid, Chemistry and Biology of Metals Laboratory @CBMLab Introduction Understanding Fur inhibition Fur dimers and tetramers Conclusion FIP-BM30A FAME-BM30B BIOSAXS-BM29 ? BioMet team, Inhibition of Fur from pathogenic bacteria: P. aeruginosa, F.tularensis and M. tuberculosis, p.2217

. Boyd, Submarine hydrothermal vents and associated gradient environments as sites for the origin and evolution of life, Origins of life and evolution of the biosphere, 1985. The History of Life: Represented on a Clock, 2014.

, Great Oxygenation events Precipitation of [Fe 2+ ] [Fe 2+ ] P(O2) Causes of GOE Life that used to have "easy" access to iron, now had to fight for it Natural selection acted in favor of tight iron regulation A

E. Massé, A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli, PNAS, 2002.