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A spectrum of changes occurs in peptidoglycan composition of glycopeptide-intermediate clinical Staphylococcus aureus
S Boyle-Vavra1, H Labischinski, C C Ebert
1Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA.
Abstract:
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.
Insights
Glycopeptide resistance in Staphylococcus aureus is not fully understood. Analysis of peptidoglycan in GISA isolates revealed no consistent structural changes, suggesting resistance isn't due to a single mechanism.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Glycopeptide resistance in Staphylococcus aureus (S. aureus) is a significant clinical concern.
- The precise mechanisms underlying glycopeptide resistance in S. aureus remain incompletely elucidated.
- Vancomycin, a key glycopeptide antibiotic, targets the D-Ala-D-Ala terminus of peptidoglycan precursors.
Purpose of the Study:
- To investigate peptidoglycan composition in clinical glycopeptide-intermediate S. aureus (GISA) isolates.
- To determine if consistent structural alterations in peptidoglycan correlate with glycopeptide resistance.
- To evaluate the role of specific peptidoglycan modifications in conferring resistance.
Main Methods:
- Muropeptides from GISA isolates were analyzed using reversed-phase high-performance liquid chromatography (RP-HPLC).
- Peptidoglycan composition was compared across various international and US-based GISA and susceptible S. aureus strains.
- Structural changes in peptidoglycan were assessed for consistency among clinical GISA isolates.
Main Results:
- While some GISA isolates (Mu50, Mu3, NJ) exhibited a large glutamate-containing monomeric peak, this was also present in some vancomycin-susceptible strains (H1) and mutants (femC).
- The presence and size of this monomeric peak varied significantly among different US GISA isolates (MI, PC, IL).
- A uniform peptidoglycan compositional alteration was not consistently observed across all GISA isolates studied.
Conclusions:
- The findings suggest that a single, uniform change in peptidoglycan composition does not account for glycopeptide resistance in all clinical GISA isolates.
- The presence of a large monomeric glutamate-containing peak is not sufficient to confer the glycopeptide resistance phenotype.
- Multiple genetic or biochemical factors likely contribute to the complex glycopeptide resistance observed in S. aureus.