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IR1 +33 1 3465 2536 mail : Karine GLOUX

Subject :

Role of prophages in the adaptation of Staphylococcus aureus to anti-FASII.

The fatty acid biosynthesis pathway (FASII) is a privileged target for new antibiotics against the major opportunistic pathogen Staphylococcus aureus. However, we showed that bacteria can circumvent these inhibitors under conditions similar to those encountered in the host. S. aureus adaptation occurs after a transitory lag without mutations in FASII genes, and is reversible. Since phages and prophages are intrinsic to bacterial diversification, we hypothesized that they might be implicated in S. aureus resistance to anti-FASII. Our first results highlight a role for S. aureus prophage in the response to anti-FASII. We are studying the mechanisms of phage contributions to anti-FASII bypass, with the goal of identifying inhibitors that in concert with the anti-FASII, would block emergence of adapted and/or resistant S. aureus.

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Bibliography (2015-2018) :

Morvan C, Halpern D, Kenanian G, Pathania A, Amba-Mondoloni J, Lamberet G, Gruss A and Gloux K (2017) The FASII bypass escape route from FASII inhibitors. Biochimie. DOI: 10.1016/j.biochi.2017.07.004.

Gloux K, Guillemet M, Soler C, Morvan C, Halpern D, Pourcel C, Thien HV, Lamberet G and Gruss A (2017). Clinical relevance of FASII bypass in Staphylococcus aureus. Antimicrob. Agents Chemother.  DOI:10.1128/AAC.02515-16.

Morvan C, Halpern D, Kenanian, G, Hays C, Amba-Mondoloni J, Brinster S, Kennedy S, Trieu-Cuot P, Poyart C, Lamberet G, Gloux K, and Gruss A (2016). Environmental Fatty Acids Enable Emergence of Infectious Staphylococcus aureus Resistant to FASII-Targeted Antimicrobials. Nat Comm. DOI: 10.1038/ncomms12944.

Gloux K, Anba-Mondoloni J. 2016. Unique beta-Glucuronidase locus in gut microbiomes of Crohn's disease patients and unaffected first-degree relatives. PLoS One 11

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