Methicillin-resistant Staphylococcus aureus (MRSA) is classically susceptible to vancomycin, but strains of vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) have arisen due to selective pressures, with the first VRSA isolated in 2002.
VISA strains often lack true inhibition mechanisms but have accumulated multiple genes conferring protection against vancomycin; though they have varied genetics they often demonstrate similar phenotype and have even been shown to occasionally revert to VSSA.
Vancomycin resistance is often conveyed by van cluster gene mutations, frequently via transformation from Enteroccocus spp. (VRE).
Vancomycin’s MoA is bactericidal via cell wall synthesis inhibition similar to the penicillins’, latching on to terminal D-Ala D-Ala moieties and stopping transpeptidation. vanA confers resistance by replacing the second D-Ala with a D-Lac, to which the vancomycin molecule has lower binding affinity. Additional van cluster mutations exist that swap D-Ala for D-Ser, like vanC.
Spread of the van genes and concern for loss of vancomycin as an effective first-line agent for Gram positive bacteria has prompted restriction of vancomycin use.
Sources: Rao et al., 2019 DeLeo et al., 2017