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Les modules de " détéction/résistance " aux antibiotiques peptidiques chez les Firmicutes

Abstract : Signal transduction systems and ABC transporters often contribute jointly to adaptive bacterial responses to environmental changes. In Bacillus subtilis, three such pairs, thereafter called modules, are involved in responses to antibiotics: BceRSAB, PsdRSAB and YxdJKLM. They are characterized by a histidine kinase belonging to the Intramembrane Sensing - Histine Kinase family (IM-HK) and by a Membrane Spanning Domain (MSD) possessing an unusually large extracytoplasmic loop. Using a phylogenomic approach we were able to demonstrate that such modules, associating a phosphorelay and an ABC transporter, are specific but widespread in Firmicutes where they originated. This analyse highlight a highly dynamic evolutionary history involving numerous horizontal gene transfers, duplications and lost events, leading to a great variety of Bce-like module repertories in members of this bacterial phylum. Based on fine phylogenetic analyses, the Bce-like modules were divided into six well-defined subfamilies. Functional studies were performed on some members of subfamily IV comprising the bacitracin resistance module BceRSAB of B. subtilis, the expression of which being found to require, in the presence of bacitracin, the signal transduction system as well as the ABC transporter itself. The present results indicate that two other members of subfamily IV, YtsCD of B. licheniformis and BceAB of B. halodurans, were also found to participate in bacitracin resistance processes. The results also suggest that in these modules the ABC transporter works as the first sensor of the antibiotic and that it then activates the signal transduction system through an interaction between one of the two ABC transporter domains and the module kinase. Bacitracin dependent expression of bceAB and bacitracin resistance processes were shown to require the presence of the BceB translocator loop suggesting a crucial role for this loop as well at a functional level, as at a structural level. This study suggests that the original BceRSAB module regulatory mechanism might be generalised to other modules and would constitute an important common antibiotic resistance mechanism in Firmicutes which comprise many human pathogens.
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https://tel.archives-ouvertes.fr/tel-00626194
Contributor : Stéphanie Coumes Florens <>
Submitted on : Friday, September 23, 2011 - 5:46:30 PM
Last modification on : Thursday, January 18, 2018 - 1:37:58 AM
Long-term archiving on: : Saturday, December 24, 2011 - 2:25:52 AM

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  • HAL Id : tel-00626194, version 1

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Stéphanie Coumes Florens. Les modules de " détéction/résistance " aux antibiotiques peptidiques chez les Firmicutes. Biologie cellulaire. Université de la Méditerranée - Aix-Marseille II, 2011. Français. ⟨tel-00626194⟩

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