The VanG-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 VanG operon, which encodes enzymes and regulatory proteins that alter the bacterial cell wall, making it resistant to vancomycin. The operon is made up of 8 genes which can be divided into regulatory (vanU, vanR and vanS), resistance (vanG, vanT and vanXY) and accessory(vanY and vanW). 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. Similar to vanR, vanU encodes for a transcriptional activator though not the primary activator. vanG 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. The accessory gene vanY, encodes a D,D-carboxypeptidase that, ensures that only D-Ala-D-Lac is used in cell wall synthesis by eliminating the terminal D-alanine residue from peptidoglycan precursorswhile vanW's function is unknown. Lastly, VanT encodes a serine racemase that is membrane-bound and supplies d-Ser for the synthesis pathway.

Vancomycin resistance pathway (vanG operon) References