A spectrum of changes occurs in peptidoglycan composition of glycopeptide-intermediate clinical Staphylococcus aureus isolates.
The mechanism of glycopeptide resistance in Staphylococcus aureus is not known with certainty. Because the target of vancomycin is the D-Ala-D-Ala terminus of the stem peptide of the peptidoglycan precursor, by subjecting muropeptides to reversed-phase high-performance liquid chromatography, we investigated peptidoglycan obtained from glycopeptide-intermediate S. aureus (GISA) isolates for changes in composition and evaluated whether any peptidoglycan structural change was a consistent feature of clinical GISA isolates. GISA isolates Mu50 and Mu3 from Japan had the large glutamate-containing monomeric peak demonstrated previously, although strain H1, a vancomycin-susceptible MRSA isolate from Japan that was clonally related to Mu3 and Mu50, and a femC mutant that we studied, did also. For the U.S. GISA isolates, strain NJ had a large monomeric peak with a retention time identical to that described for the glutamate-containing monomer in strains H1, Mu3, and Mu50. However, a much smaller corresponding peak was seen in GISA MI, and this peak was absent from both GISA PC and a recent GISA isolate obtained from an adult patient in Illinois (strain IL). These data suggest that a uniform alteration in peptidoglycan composition cannot be discerned among the GISA isolates and indicate that a single genetic or biochemical change is unlikely to account for the glycopeptide resistance phenotype in the clinical GISA isolates observed to date. Furthermore, a large monomeric glutamate-containing peak is not sufficient to confer the resistance phenotype.
Boyle-Vavra
S
S
Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA.
Labischinski
H
H
Ebert
C C
CC
Ehlert
K
K
Daum
R S
RS
D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004352:Drug Resistance, Microbial; D008826:Microbial Sensitivity Tests; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism*; D017334:Teicoplanin / Q000378:metabolism / Q000494:pharmacology; D014640:Vancomycin / Q000378:metabolism / Q000494:pharmacology; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D017334:Teicoplanin; D014640:Vancomycin