{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:13:45Z","timestamp":1791299625592,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,7,12]],"date-time":"2013-07-12T00:00:00Z","timestamp":1373587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2013,8]]},"abstract":"Summary<\/jats:title>vanGCd<\/jats:sub><\/jats:italic><\/jats:styled-content>, a cryptic gene cluster highly homologous to the vanG<\/jats:italic><\/jats:styled-content> gene cluster of E<\/jats:styled-content>nterococcus faecalis<\/jats:italic> is largely spread in C<\/jats:styled-content>lostridium difficile<\/jats:italic>. Since emergence of vancomycin resistance would have dramatic clinical consequences, we have evaluated the capacity of the vanGCd<\/jats:sub><\/jats:italic><\/jats:styled-content> cluster to confer resistance. We showed that expression of vanGCd<\/jats:sub><\/jats:italic><\/jats:styled-content> is inducible by vancomycin and that VanGCd<\/jats:sub><\/jats:styled-content>, VanXYCd<\/jats:sub><\/jats:styled-content> and VanTCd<\/jats:sub><\/jats:styled-content> are functional, exhibiting D<\/jats:styled-content>\u2010A<\/jats:styled-content>la\u2009:\u2009D<\/jats:styled-content>\u2010S<\/jats:styled-content>er ligase, D<\/jats:styled-content>,D<\/jats:styled-content>\u2010dipeptidase and D<\/jats:styled-content>\u2010S<\/jats:styled-content>er racemase activities respectively. In other bacteria, these enzymes are sufficient to promote vancomycin resistance. Trans\u2010complementation of C<\/jats:styled-content>.\u2009difficile<\/jats:italic> with the vanC<\/jats:italic><\/jats:styled-content> resistance operon of E<\/jats:styled-content>nterococcus gallinarum<\/jats:italic> faintly impacted the MIC<\/jats:styled-content> of vancomycin, but did not promote vancomycin resistance in C<\/jats:styled-content>.\u2009difficile<\/jats:italic>. Sublethal concentration of vancomycin led to production of UDP<\/jats:styled-content>\u2010MurNAc<\/jats:styled-content>\u2010pentapeptide[D\u2010Ser<\/jats:styled-content>], suggesting that the vanGCd<\/jats:sub><\/jats:italic><\/jats:styled-content> gene cluster is able to modify the peptidoglycan precursors. Our results indicated amidation of UDP<\/jats:styled-content>\u2010MurNAc<\/jats:styled-content>\u2010tetrapeptide, UDP<\/jats:styled-content>\u2010MurNAc<\/jats:styled-content>\u2010pentapeptide[D\u2010Ala<\/jats:styled-content>] and UDP<\/jats:styled-content>\u2010MurNAc<\/jats:styled-content>\u2010pentapeptide[D<\/jats:styled-content>\u2010S<\/jats:styled-content>er]. This modification is passed on the mature peptidoglycan where a muropeptide Tetra\u2010Tetra is amidated on the meso<\/jats:italic><\/jats:styled-content>\u2010diaminopimelic acid. Taken together, our results suggest that the vanGCd<\/jats:sub><\/jats:italic><\/jats:styled-content> gene cluster is functional and is prevented from promoting vancomycin resistance in C<\/jats:styled-content>.\u2009difficile<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/mmi.12299","type":"journal-article","created":{"date-parts":[[2013,6,20]],"date-time":"2013-06-20T10:50:21Z","timestamp":1371725421000},"page":"612-625","source":"Crossref","is-referenced-by-count":58,"title":["The functional vanGCd<\/sub><\/i><\/scp> cluster of C<\/scp>lostridium difficile<\/i> does not confer vancomycin resistance"],"prefix":"10.1111","volume":"89","author":[{"given":"Fariza","family":"Ammam","sequence":"first","affiliation":[{"name":"EA4043 Facult\u00e9 de Pharmacie Universit\u00e9 Paris Sud Ch\u00e2tenay\u2010Malabry France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djalal","family":"Meziane\u2010cherif","sequence":"additional","affiliation":[{"name":"Institut Pasteur Unit\u00e9 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