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Resistance and virulence of Pseudomonas aeruginosa clinical strains overproducing the MexCD-OprJ efflux pump

Jeannot, Katy
Elsen, Sylvie
Attree, Ina
Plesiat, Patrick
Published in Antimicrobial agents and chemotherapy. 2008, vol. 52, no. 7, p. 2455-2462
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 microg/ml to 4 microg/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 AdultAgedAnti-Bacterial Agents/pharmacologyBacterial Proteins/biosynthesis/geneticsBase SequenceCiprofloxacin/pharmacologyDNA Primers/geneticsDNA, Bacterial/geneticsDNA-Binding Proteins/biosynthesis/geneticsDrug Resistance, Bacterial/genetics/physiologyFemaleGenes, BacterialHumansMaleMembrane Proteins/biosynthesis/geneticsMembrane Transport Proteins/biosynthesis/geneticsMiddle AgedMolecular Sequence DataMutationPseudomonas Infections/drug therapy/microbiologyPseudomonas aeruginosa/ drug effects/genetics/metabolism/ pathogenicityTranscription Factors/biosynthesis/geneticsVirulence/genetics/physiology
PMID: 18474583
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JEANNOT, Katy et al. Resistance and virulence of Pseudomonas aeruginosa clinical strains overproducing the MexCD-OprJ efflux pump. In: Antimicrobial agents and chemotherapy, 2008, vol. 52, n° 7, p. 2455-2462. doi: 10.1128/AAC.01107-07 https://archive-ouverte.unige.ch/unige:7354

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Deposited on : 2010-06-21

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