High‐Level Fluoroquinolone Resistance in Pseudomonas aeruginosa Due to Interplay of the MexAB‐OprM Efflux Pump and the DNA Gyrase Mutation

@article{Nakajima2002HighLevelFR,
  title={High‐Level Fluoroquinolone Resistance in Pseudomonas aeruginosa Due to Interplay of the MexAB‐OprM Efflux Pump and the DNA Gyrase Mutation},
  author={Akira Nakajima and Yohko Sugimoto and Hiroshi Yoneyama and Taiji Nakae},
  journal={Microbiology and Immunology},
  year={2002},
  volume={46}
}
Fluoroquinolone resistance in Pseudomonas aeruginosa is mainly attributable to the constitutive expression of the xenobiotic efflux pump and mutation in DNA gyrase or topoisomerase IV. We constructed cells with a double‐mutation in gyrA and mexR encoding DNA gyrase and repressor for the mexAB‐oprM operon, respectively. The mutant showed 1,024 times higher fluoroquinolone resistance than cells lacking the MexAB‐OprM. Cells with a single mutation in gyrA and producing a wild‐type level of the… 
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It is demonstrated that multidrug resistance to the fluoroquinolones and carbapenems in these clinical isolates was not a result of the overexpression of the mexEF-oprN pump, and instead, resistance to these two agents seemed to arise through independent mutational events.

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A high level of antimicrobial resistance may have been due to the coexistence of different resistance mechanisms among the studied P. aeruginosa strains, however, this does not exclude the contribution of the MexAB‐OprM pump, particularly in resistance to meropenem and ciprofloxacin.

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It is suggested that the co-administration of an EPI with FQs or other antibiotics currently in use would not be sufficient to combat the complexity of resistance mechanisms now present in many clinical isolates.

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This is the first report of efflux pump mediated FQ resistance from this part of the world and the continued emergence of these mutants with such high MIC range from this region demands serious awareness, diagnostic intervention, and proper therapeutic option.

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The most frequently detected mutation in the gyrA gene (16 out of 25 mutants) was the Thr-83 --> Ile substitution, which led to the following amino acid replacements in Pseudomonas aeruginosa.

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Studies of quinolones can address most aspects of antibiotic resistance, and batteries of resistant mutants can be used to identify compounds that have a very narrow selection window and are likely to restrict the emergence of resistance.
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