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KMID : 0043319950180030173
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Archives of Pharmacal Research
1995 Volume.18 No. 3 p.173 ~ p.178
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Ciprofloxacin Resistance by Altered Gyrase and Drug Efflux System in Pseudomonas aeruginosa
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Cho Myung-Sun
Kim Do-Yeob
Kong Jae-Yang
Yang Sung-Il
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Abstract
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Ciprofloxacin resistance mechanisms were studied by investigating the inhibitory effect of ciprofloxacin on the gyrase-mediated DNA supercoiling and the intracellular accumulation of ciprofloxacin in clinical isolates of Pseudomonas aeruginosa. A higher amount of ciprofloxacin was required to inhibit the gyrases purified from the ciprofloxacin-resistant strains than that from the sensitive strain. Reconstitution of heterologous gyrase subunits from different strains revealed alterations in the A and/or the B subunits of gyrase in these strains. In addition, the resistant strains accumulated approximately a half amount of ciprofloxacin inside the cells, compared to the sensitive strain. However, when the active efflux was blocked by carbonyl cyanide m-chlorophenyl hydrazone treatment, intracellular concentration of ciprofloxacin was elevated about 4-7 fold in these strains, while the sensitive strain was not significantly affected by this treatment, indicating that the ciprofloxacin-resistant strains developed a drug efflux system. Interestingly, these resistant strains expressed an envelope protein of approximately 51 kD. These studies suggest that alterations in the gyrase as well as the active drug-efflux system conferred dual ciprofloxacin resistance mechanisms to these clinical isolates of P. aeruginosa.
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KEYWORD
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Ciprofloxacin, Resistance, Gyrase, Efflux, Pseudomonas aeruginosa
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