Decreased membrane permeability in a polymyxin B-resistant Escherichia coli mutant exhibiting multiple resistance to beta-lactams as well as aminoglycosides.
A laboratory mutant of Escherichia coli stably resistant to more than 36,000 U ml-1 of polymyxin B was isolated. The mutant exhibited moderate increases in minimum inhibitory concentration to fluoroquinolones and bacitracin but high levels of cross-resistance to beta-lactams and aminoglycosides. However, it remained susceptible to tetracycline, nalidixic acid and novobiocin. Changes were observed in the outer membrane proteins and lipopolysaccharide profile leading to a decrease in permeability as evident from reduction in the following: (i) minimum inhibitory concentration values in the presence of Tween 80, (ii) uptake of 1-N-phenyl naphthylamine and norfloxacin, (iii) hydrolysis of beta-lactams and (iv) diffusion of lactose and cefazolin into proteoliposomes reconstituted with outer membrane proteins. We therefore suggest that the novel pattern of cross-resistance of our isolate is due to the decrease in its permeability.
Rahaman
S O
SO
Department of Life Science and Biotechnology, Jadavpur University, Calcutta, India.
Mukherjee
J
J
Chakrabarti
A
A
Pal
S
S
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000493:pharmacokinetics; D001425:Bacterial Outer Membrane Proteins / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004352:Drug Resistance, Microbial / Q000502:physiology; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D008070:Lipopolysaccharides; D009154:Mutation; D009643:Norfloxacin / Q000493:pharmacokinetics; D011112:Polymyxin B / Q000494:pharmacology; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides; D047090:beta-Lactams; D011112:Polymyxin B; D009643:Norfloxacin