Cell-wall thickness: possible mechanism of acriflavine resistance in meticillin-resistant Staphylococcus aureus.
Acriflavine resistance in the clinical meticillin-resistant Staphylococcus aureus isolate KT24 was found not to be mediated by multidrug efflux pumps encoded by qacA/B, smr, qacE, qacG, qacH, qacJ or norA. Early uptake and accumulation of ethidium bromide in MRSA KT24 was significantly lower than that in a susceptible strain, although the efflux rates were similar. Therefore, a permeability barrier in MRSA KT24 may be the conceivable mechanism of acriflavine resistance. Interestingly, it was found that MRSA KT24 had a significantly thickened cell wall, and that cell-wall thickness increased gradually during bacterial growth. In contrast, cell size and surface area in MRSA KT24 were not different from those in the susceptible strain. Moreover, MRSA KT24 exposure to sub-MIC concentrations of acriflavine resulted in a thicker cell wall. These results indicate that cell-wall thickness may be responsible for acriflavine resistance in S. aureus.
Kawai
Mako
M
Microbiological Control Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co. Ltd, 5-51 Ebie 1-chome Fukushima-ku, Osaka 553-0001, Japan.
Yamada
Sakuo
S
Department of Clinical Nutrition, Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki, Okayama 701-0193, Japan.|Department of Microbiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Ishidoshiro
Ai
A
Quality Assurance Group, Ibaraki Manufacturing Plant, Dainippon Sumitomo Pharma Co. Ltd, 3-45 1-chome Kurakakiuchi, Ibaraki, Osaka 567-0878, Japan.
Oyamada
Yoshihiro
Y
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd, Enoki, 33-94 Suita, Osaka 564-0053, Japan.
Ito
Hideaki
H
Pharmacovigilance, Dainippon Sumitomo Pharma Co. Ltd, 6-8 Doshomachi 2-Chome, Chuo-ku, Osaka 541-0045, Japan.
Yamagishi
Jun-Ichi
JI
Microbiological Control Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co. Ltd, 5-51 Ebie 1-chome Fukushima-ku, Osaka 553-0001, Japan.
D000167:Acriflavine / Q000378:metabolism / Q000494:pharmacology*; D000891:Anti-Infective Agents, Local / Q000378:metabolism / Q000494:pharmacology*; D017920:Antiporters / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D024881:Drug Resistance, Bacterial / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission
D000891:Anti-Infective Agents, Local; D017920:Antiporters; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C099272:QacB protein, Staphylococcus aureus; C521590:small multidrug-resistance pump, Staphylococcus aureus; C068498:qacA protein, Staphylococcus aureus; D000167:Acriflavine