Increase in glutamine-non-amidated muropeptides in the peptidoglycan of vancomycin-resistant Staphylococcus aureus strain Mu50.
The peptidoglycan compositions of vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50 (MIC 8 mg/L) and hetero-VRSA strain Mu3 (MIC 3 mg/L) were compared in order to understand the mechanism of vancomycin resistance. As compared with Mu3, the cell wall of Mu50 had increased amounts of glutamine-non-amidated muropeptides and decreased cross-linking of peptidoglycan with a greatly decreased dimer/monomer ratio of muropeptides. In agreement with this observation, the peptidoglycan of Mu50 bound 1.4 times more vancomycin than that of Mu3. The increase in non-amidated muropeptides and the reduced cross-linking of the cell-wall peptidoglycan may contribute to the vancomycin resistance by increasing the consumption of vancomycin by the pre-existing cell wall of Mu50 and reducing the amount of vancomycin reaching the cytoplasmic membrane where the vital targets of the antibiotic are situated.
Hanaki
H
H
Department of Bacteriology, Juntendo University, Tokyo, Japan.
Labischinski
H
H
Inaba
Y
Y
Kondo
N
N
Murakami
H
H
Hiramatsu
K
K
D000596:Amino Acids / Q000032:analysis; D004352:Drug Resistance, Microbial; D005973:Glutamine / Q000737:chemistry / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism*; D010641:Phenotype; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D014640:Vancomycin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D000596:Amino Acids; D010455:Peptides; D010457:Peptidoglycan; D005973:Glutamine; D014640:Vancomycin