Resistance and Virulence of Pseudomonas aeruginosa Clinical Strains Overproducing the MexCD-OprJ Efflux Pump
- 1 July 2008
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 52 (7), 2455-2462
- https://doi.org/10.1128/aac.01107-07
Abstract
Since their initial description 2 decades ago, MexCD-OprJ-overproducing efflux mutants of Pseudomonas aeruginosa (also called nfxB mutants) have rarely been described in the clinical setting. Screening of 110 nonreplicate clinical isolates showing moderate resistance to ciprofloxacin (MIC from 0.5 μg/ml to 4 μg/ml) yielded only four mutants (3.6%) of that type harboring various alterations in the repressor gene nfxB . MexCD-OprJ upregulation correlated with an increased resistance to ciprofloxacin, cefepime, and chloramphenicol in most of the clinical strains, concomitant with a higher susceptibility to ticarcillin, aztreonam, imipenem, and aminoglycosides. Evidence was obtained that this increased susceptibility to aminoglycosides results from the impaired activity of efflux pump MexXY-OprM. Furthermore, MexCD-OprJ upregulation was found to impair bacterial growth and to have a strain-specific, variable impact on rhamnolipid, elastase, phospholipase C, and pyocyanin production. Review of patient files indicated that the four nfxB mutants were responsible for confirmed cases of infection and emerged during long-term therapy with ciprofloxacin. Taken together, these data show that, while rather infrequent among P. aeruginosa strains with low-level resistance to ciprofloxacin, MexCD-OprJ-overproducing mutants may be isolated after single therapy with fluoroquinolones and may be pathogenic.Keywords
This publication has 61 references indexed in Scilit:
- Relationship between Antibiotic Use and Incidence of MexXY-OprM Overproducers among Clinical Isolates of Pseudomonas aeruginosaAntimicrobial Agents and Chemotherapy, 2008
- Pseudomonas aeruginosa May Accumulate Drug Resistance Mechanisms without Losing Its Ability To Cause Bloodstream InfectionsAntimicrobial Agents and Chemotherapy, 2007
- MexAB-OprM- and MexXY-Overproducing Mutants Are Very Prevalent among Clinical Strains of Pseudomonas aeruginosa with Reduced Susceptibility to TicarcillinAntimicrobial Agents and Chemotherapy, 2007
- Development and Persistence of Antimicrobial Resistance in Pseudomonas aeruginosa : a Longitudinal Observation in Mechanically Ventilated PatientsAntimicrobial Agents and Chemotherapy, 2007
- Cumulative Effects of Several Nonenzymatic Mechanisms on the Resistance of Pseudomonas aeruginosa to AminoglycosidesAntimicrobial Agents and Chemotherapy, 2007
- Involvement of the MexXY-OprM Efflux System in Emergence of Cefepime Resistance in Clinical Strains of Pseudomonas aeruginosaAntimicrobial Agents and Chemotherapy, 2006
- A 10-min method for preparation of highly electrocompetent Pseudomonas aeruginosa cells: Application for DNA fragment transfer between chromosomes and plasmid transformationJournal of Microbiological Methods, 2006
- Induction of the MexXY Efflux Pump in Pseudomonas aeruginosa Is Dependent on Drug-Ribosome InteractionJournal of Bacteriology, 2005
- Cloning and nucleotide sequence of thePseudomonas aeruginosa nfxBgene, conferring resistance to new quinolonesFEMS Microbiology Letters, 1992
- Genetic Recombination in Pseudomonas aeruginosaMicrobiology, 1955