[Mechanism of vancomycin resistance in MRSA strain Mu50].
The mechanism of vancomycin resistance in methicillin-resistant Staphylococcus aureus (MRSA) Mu50 was investigated. More than 3 times increase of the incorporation of 14C-GluNAc into the cell wall of Mu50 was observed compared to those of vancomycin-susceptible strains FDA209P, H-1, LR5P1. The amount of cytoplasmic murein-monomer precursor increased more than 3 times in Mu50 compared to those of control strains. There was an increased production of PBP1, PBP2, and PBP2', which were 1.51, 17.2, and 7.06 times greater, respectively, in Mu50 than those in H-1, and 2.38, 4.46, and 1.96 times greater respectively, than those in LR5P1. By transmission electromicrograph, it was shown that the cell wall of Mu50 was twice thicker than that of LR5P1. Increase of tightly-bound vancomycin to the cell wall fraction was observed in Mu50 when compared to those in FDA209P and H-1 strains. From these results, the increase of the vancomycin targets, free D-Ala-D-Ala residues in the cell wall, in number, due to the activated cell wall synthesis, and/or decrease of the cross-linkage of the cell wall was suggested to be the mechanism of vancomycin resistance in the Mu50 strain.
Hanaki
H
H
Dept. Bacteriology, Juntendo-Univ., Tokyo, Japan.
Labischinski
H
H
Sasaki
K
K
Kuwahara-Arai
K
K
Inaba
Y
Y
Hiramatsu
K
K
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism / Q000648:ultrastructure; D004352:Drug Resistance, Microbial; D006602:Hexosyltransferases; D006801:Humans; D016106:Methicillin Resistance; D017348:Microscopy, Electron, Scanning Transmission; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000378:metabolism; D010458:Peptidyl Transferases; D011023:Pneumonia, Staphylococcal / Q000382:microbiology; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013530:Surgical Wound Infection / Q000382:microbiology; D014640:Vancomycin / Q000378:metabolism / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D014640:Vancomycin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase