VanA gene

Vancomycin normally works by binding the terminal D-Ala-D-Ala of the peptidoglycan pentapeptide, sterically blocking transglycosylation and transpeptidation. The vanA operon encodes enzymes that synthesize a depsipeptide ending in D-Ala-D-Lac and destroy the normal precursor, eliminating a critical hydrogen bond and abolishing binding; vanA confers resistance to both vancomycin and teicoplanin, whereas vanB confers vancomycin resistance with retained teicoplanin activity. Because vanA sits on a transposon within a conjugative plasmid, it spreads readily, and its transfer from Enterococcus faecium to Staphylococcus aureus has produced the rare but serious vancomycin-resistant S. aureus. Risk factors for VRE colonization are prolonged hospitalization, prior vancomycin or cephalosporin exposure, and intensive care. Treatment options for VRE include linezolid, an oxazolidinone that inhibits the 50S subunit and can cause thrombocytopenia and serotonin syndrome with SSRIs, and daptomycin, a lipopeptide that depolarizes the membrane, causes myopathy with raised creatine kinase, and is inactivated by pulmonary surfactant so cannot be used for pneumonia.