In vitro antibacterial activities of tosufloxacin against and uptake of tosufloxacin by outer membrane mutants of Escherichia coli, Proteus mirabilis, and Salmonella typhimurium.

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RESUMO

The antibacterial activities of tosufloxacin and other quinolones against and apparent uptakes of tosufloxacin and other quinolones by outer membrane mutants of Escherichia coli, Proteus mirabilis, and Salmonella typhimurium were studied. The hydrophobicity of tosufloxacin was nearly equal to that of ofloxacin or lower than those of sparfloxacin and nalidixic acid. OmpF- and OmpC-deficient E. coli and 40-kDa porin-deficient P. mirabilis mutants were twofold more susceptible to tosufloxacin and sparfloxacin but two- to fourfold less susceptible to other quinolones than their parent strains. In S. typhimurium lipopolysaccharide-deficient (rough) mutants, the differences in susceptibility to tosufloxacin were similar to those to sparfloxacin and nalidixic acid. The apparent uptake of tosufloxacin by intact cells was increased in porin-deficient mutants compared with that by their parent strain. These results suggest that the permeation route of tosufloxacin across the outer membrane is different from that of other fluoroquinolones and that tosufloxacin may permeate mainly through the nonporin pathway, presumably phospholipid bilayers. However, this characteristic is independent of the hydrophobicity of the molecule.

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