[Increase of non-amidated muropeptides in the cell wall of vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50].
The mechanism of resistance was studied with vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50. It was demonstrated that the incorporation of 14C-N-acetylglucosamine into the cell wall of Mu50 was not suppressed in the presence of 8 microliters/ml of vacomycin, whereas it was completely suppressed in vancomycin-susceptible strains FDA209P and H-1. Increased binding of vancomycin to the wall of Mu50 was observed compared to the control strains: 1.7 x 10(16) (Mu50), 6.1 x 10(15) (209P), and 6.7 x 10(15) (H-1) vancomycin molecules/mg cell wall, respectively. Remarkable proportion of the cell-wall component muropeptides were non-amidated in the cell wall of Mu50. In concordance with this phenomena, peptidoglycan cross-linkage decreased strikingly in the Mu50 strain. Free D-Ala-D-Ala residues at the end of muropeptides in the pre-existing cell wall generated by decreased cross-linkage seems to account for increased vancomycin binding. The increase of vancomycin-resistance level is presumably caused by sequestration of vancomycin molecules from primary target point on cell membrane. It was considered that at least two phenotypic changes are required for the vancomycin resistance in the Mu50 strain. First, as we have described previously, is the activated cell wall synthesis, and second, the reduction of cross-linkage of peptidoglycan by production of non-amidated muropeptide precursors.
Hanaki
H
H
Dept. Bacteriology, Juntendo-Univ., Tokyo, Japan.
Labischinski
H
H
Inaba
Y
Y
Hiramatsu
K
K
D000117:Acetylglucosamine / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002473:Cell Wall / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D006801:Humans; D010457:Peptidoglycan / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D014640:Vancomycin / Q000493:pharmacokinetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D014640:Vancomycin; D000117:Acetylglucosamine