The VanC-type vancomycin resistance pathway enables enterococcal bacteria to resist the action of the glycopeptide antibiotic vancomycin. This pathway involves a series of genes organized in an the VanC operon, which encodes enzymes and regulatory proteins that alter the bacterial cell wall, making it resistant to vancomycin. The operon is made up of 5 genes which can be divided into regulatory (vanR and vanS) and resistance (vanC, vanT and vanXY). The vanR gene is a response regulator that is part of a two-component regulatory system and activates transcription once phosphorylated by histidine kinase that is encoded by vanS, after detecting vancomycin. vanC gene encodes a D-Ala-D-Ser ligase, which synthesizes D-Ala-D-Ser (D-alanine-D-serine) dipeptides instead of the usual D-Ala-D-Ala in the peptidoglycan precursor, which has reduced affinity for vancomycin and is added to UDP-MurNAc-tripeptide.vanXY gene encodes a bifunctional D,D-dipeptidase and D,D-carboxypeptidase that hydrolyzes any remaining D-Ala-D-Ala dipeptides and removes D-alanine from peptidoglycan precursors (UDP-MurNAc-pentapeptide[d-Ala]), ensuring that only D-Ala-D-Ser is incorporated into the cell wall. Lastly, VanT encodes a serine racemase that is membrane-bound and supplies d-Ser for the synthesis pathway.

Vancomycin resistance pathway (VanC operon) References