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- Title
The functional vanG<sub>Cd</sub> cluster of Clostridium difficile does not confer vancomycin resistance.
- Authors
Ammam, Fariza; Meziane‐cherif, Djalal; Mengin‐Lecreulx, Dominique; Blanot, Didier; Patin, Delphine; Boneca, Ivo G.; Courvalin, Patrice; Lambert, Thierry; Candela, Thomas
- Abstract
vanGCd, a cryptic gene cluster highly homologous to the vanG gene cluster of Enterococcus faecalis is largely spread in Clostridium difficile. Since emergence of vancomycin resistance would have dramatic clinical consequences, we have evaluated the capacity of the vanGCd cluster to confer resistance. We showed that expression of vanGCd is inducible by vancomycin and that VanGCd, VanXYCd and VanTCd are functional, exhibiting D- Ala : D- Ser ligase, D, D-dipeptidase and D- Ser racemase activities respectively. In other bacteria, these enzymes are sufficient to promote vancomycin resistance. Trans-complementation of C. difficile with the vanC resistance operon of Enterococcus gallinarum faintly impacted the MIC of vancomycin, but did not promote vancomycin resistance in C. difficile. Sublethal concentration of vancomycin led to production of UDP- MurNAc-pentapeptide[ D-Ser], suggesting that the vanGCd gene cluster is able to modify the peptidoglycan precursors. Our results indicated amidation of UDP- MurNAc-tetrapeptide, UDP- MurNAc-pentapeptide[ D-Ala] and UDP- MurNAc-pentapeptide[ D- Ser]. This modification is passed on the mature peptidoglycan where a muropeptide Tetra-Tetra is amidated on the meso-diaminopimelic acid. Taken together, our results suggest that the vanGCd gene cluster is functional and is prevented from promoting vancomycin resistance in C. difficile.
- Subjects
ENTEROCOCCUS faecalis; GENES; VANCOMYCIN resistance; GLYCOPEPTIDES; GRAM-positive bacteria; PATHOGENIC microorganisms
- Publication
Molecular Microbiology, 2013, Vol 89, Issue 4, p612
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/mmi.12299