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 Y 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… Expand
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TLDR
The results show that antibiotic and metabolic stress lead to up-regulation of Mex EF-OprN expression via different mechanisms and that MexEF-OPRN does not only extrude antimicrobials but rather serves other important metabolic functions. Expand
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TLDR
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. Expand
Multidrug resistance associated with mexXY expression in clinical isolates of Pseudomonas aeruginosa from a Texas hospital.
TLDR
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. Expand
Expression of MexAB‐OprM efflux pump system and susceptibility to antibiotics of different Pseudomonas aeruginosa clones isolated from patients hospitalized in two intensive care units at University Hospital in Bialystok (northeastern Poland) between January 2002 and December 2009
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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. Expand
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The modeled structure of the fusion protein shows that the position and orientation of the N-terminal fused EGFP domain may either partially block the translocation pore or restrict the movement of the individual pump domains, which may lead to partially restricted efflux activity. Expand
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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. Expand
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In the future, efflux pump inhibitors may offer effective adjunctive therapy to antibiotics for the treatment of difficult infections by efflux mutants, and appropriate antibiotic selection and optimal dosing strategies should aim to eradicate the causative pathogen before a resistant efflux mutant can emerge. Expand
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TLDR
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. Expand
Carbapenem-resistance mechanisms of multidrug-resistant Pseudomonas aeruginosa.
TLDR
Pulsed-field gel electrophoresis showed high genomic homogeneity of these isolates and confirmed the circulation of an endemic clone belonging to serotype O4, and meropenem accumulation was slightly higher in bacilli than in the filamentous cells that formed in the presence of antibiotics. Expand
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