Virginiamycin acetyltransferase VatD (VatD)

Virginiamycin acetyltransferase VatD is a bacterial enzyme that confers resistance to streptogramin A-type antibiotics, such as virginiamycin M1 and dalfopristin (UniProt P50870). Primarily identified in Enterococcus faecium, this enzyme belongs to the xenobiotic acetyltransferase (XAT) family and functions as a homotrimer with a characteristic left-handed beta-helix fold (PubMed: 11846601). Its mechanism involves the O-acetylation of the antibiotic's C14 hydroxyl group using acetyl-CoA as a cofactor, which sterically prevents the antibiotic from binding to its target site on the bacterial 50S ribosome (PubMed: 24413462). This enzymatic inactivation is a major clinical challenge, as it neutralizes last-resort treatments for multi-drug resistant Gram-positive infections (CARD ARO:3002843). VatD is frequently encoded on mobile genetic elements like plasmids, allowing for rapid dissemination across bacterial populations (PubMed: 12771141). Consequently, it is a key target for research into resistance-breaking compounds, including modified streptogramins that evade acetylation and potential inhibitors designed to restore the efficacy of existing antibiotic combinations like quinupristin/dalfopristin (PubMed: 32581358).

Other names

Streptogramin A acetyltransferaseSatAVirginiamycin A acetyltransferase DVat(D)

VatD inactivates streptogramin A antibiotics by catalyzing the transfer of an acetyl group from acetyl-CoA to the C14 hydroxyl group of the antibiotic, which sterically hinders the antibiotic's ability to bind to the 50S ribosomal subunit and inhibit protein synthesis (PubMed: 11846601, 24413462).