title: High level oxacillin and vancomycin resistance and altered cell wall composition in Staphylococcus aureus carrying the staphylococcal mecA and the enterococcal vanA gene complex.
abstract: Recently, for the first time in the history of this bacterial species, methicillin-resistant Staphylococcus aureus (MRSA) carrying the enterococcal vanA gene complex and expressing high level resistance to vancomycin was identified in clinical specimens (CDC (2002) MMWR 51, 565-567). The purpose of our studies was to understand how vanA is expressed in the heterologous background of S. aureus and how it interacts with the mecA-based resistance mechanism, which is also present in these strains and is targeted on cell wall biosynthesis. The vanA-containing staphylococcal plasmid was transferred from the clinical vancomycin-resistant S. aureus (VRSA) strain HIP11714 (CDC (2002) MMWR 51, 565-567) to the methicillin-resistant S. aureus (MRSA) strain COL for which extensive genetic and biochemical information is available on staphylococcal cell wall biochemistry and drug resistance mechanisms. The transconjugant named COLVA showed high and homogeneous resistance to both oxacillin and vancomycin. COLVA grown in vancomycin-containing medium produced an abnormal peptidoglycan: all pentapeptides were replaced by tetrapeptides, and the peptidoglycan contained at least 22 novel muropeptide species that frequently showed a deficit or complete absence of pentaglycine branches. The UDP-MurNAc-pentapeptide, the major component of the cell wall precursor pool in vancomycin-sensitive cells was replaced by UDP-MurNAc-depsipeptide and UDP-MurNAc-tetrapeptide. Transposon inactivation of the beta-lactam resistance gene mecA caused complete loss of beta-lactam resistance but had no effect on the expression of vancomycin resistance. The two major antibiotic resistance mechanisms encoded by mecA and vanA residing in the same S. aureus appear to use different sets of enzymes for the assembly of cell walls.
authors: The Rockefeller University, New York, New York 10021, USA.
authors: Anatoly
authors: A
authors: Severin
authors: Keiko
authors: K
authors: Tabei
authors: Fred
authors: F
authors: Tenover
authors: Marilyn
authors: M
authors: Chung
authors: Nancy
authors: N
authors: Clarke
authors: Alexander
authors: A
authors: Tomasz
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D019729:Carbon-Oxygen Ligases / Q000235:genetics*; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004352:Drug Resistance, Microbial; D016983:Enterococcus / Q000378:metabolism*; D007769:Lactams / Q000737:chemistry; D013058:Mass Spectrometry; D008956:Models, Chemical; D009876:Operon; D010068:Oxacillin / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D010457:Peptidoglycan / Q000737:chemistry; D013211:Staphylococcus aureus / Q000378:metabolism*; D013997:Time Factors; D014640:Vancomycin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007769:Lactams; D010455:Peptides; D010457:Peptidoglycan; C071437:VanA ligase, Bacteria; C083616:mecA protein, Bacillus subtilis; D014640:Vancomycin; D019729:Carbon-Oxygen Ligases; D010068:Oxacillin