Decreased membrane permeability in a polymyxin B-resistantEscherichia colimutant exhibiting multiple resistance to β-lactams as well as aminoglycosides

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Abstract
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 β-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 β-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.