title: Mechanisms of vancomycin resistance in Staphylococcus aureus.
abstract: Vancomycin is a glycopeptide antibiotic used for the treatment of Gram-positive bacterial infections. Traditionally, it has been used as a drug of last resort; however, clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) strains with decreased susceptibility to vancomycin (vancomycin intermediate-resistant S. aureus [VISA]) and more recently with high-level vancomycin resistance (vancomycin-resistant S. aureus [VRSA]) have been described in the clinical literature. The rare VRSA strains carry transposon Tn1546, acquired from vancomycin-resistant Enterococcus faecalis, which is known to alter cell wall structure and metabolism, but the resistance mechanisms in VISA isolates are less well defined. Herein, we review selected mechanistic aspects of resistance in VISA and summarize biochemical studies on cell wall synthesis in a VRSA strain. Finally, we recapitulate a model that integrates common mechanistic features of VRSA and VISA strains and is consistent with the mode of action of vancomycin.
authors.forename: Susana
authors.initials: S
authors.lastname: Gardete
authors.forename: Alexander
authors.initials: A
authors.lastname: Tomasz
mesh_terms: D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004251:DNA Transposable Elements / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009154:Mutation; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020713:Vancomycin Resistance / Q000235:genetics / Q000502:physiology; D014774:Virulence / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D004269:DNA, Bacterial