ArticleAntimicrobial agents and chemotherapy2013
Quantitative contributions of target alteration and decreased drug accumulation to Pseudomonas aeruginosa fluoroquinolone resistance.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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89 citing papers in PubMed, 142 citations in OpenAlex.
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- Resistance Response and Regulatory Mechanisms of Ciprofloxacin-Induced ResistantAntibiotics (Basel, Switzerland) · 2025Article
- Exploring the potential role of GyrA inhibiting quinoline analog: an in silico study.Scientific reports · 2025Article
- Ciprofloxacin resistance rapidly declines in nfxB defective clinical strains of Pseudomonas aeruginosa.Nature communications · 2025Article
- Import of global high-risk clones is the primary driver of carbapenemase-producingJournal of medical microbiology · 2025Article
- Fluoroquinolone resistance in ESKAPE pathogens: evolutionary pathways, one health transmission, and clinical surveillance.Frontiers in microbiology · 2025Review
- Genomic and phenotypic characterisation ofFrontiers in microbiology · 2025Article
- Pathogenomic Insights intoLife (Basel, Switzerland) · 2024Article
- Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation.JAC-antimicrobial resistance · 2024Review
- Impact of multidrug resistance on the virulence and fitness of Pseudomonas aeruginosa: a microbiological and clinical perspective.Infection · 2024Review
- Unveiling the microevolution of antimicrobial resistance in selected Pseudomonas aeruginosa isolates from Egyptian healthcare settings: A genomic approach.Scientific reports · 2024Article
- Keeping up with the pathogens: improved antimicrobial resistance detection and prediction from Pseudomonas aeruginosa genomes.Genome medicine · 2024Article
- Quorum-sensing regulation of phenazine production heightensAntimicrobial agents and chemotherapy · 2024Article
29 more citing papers are in PubMed but not listed here.
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5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quinolone antibiotics constitute a clinically successful and widely used class of broad-spectrum antibiotics; however, the emergence and spread of resistance increasingly limits the use of fluoroquinolones in the treatment and management of microbial disease. In this study, we evaluated the quantitative contributions of quinolone target alteration and efflux pump expression to fluoroquinolone resistance in Pseudomonas aeruginosa. We generated isogenic mutations in hot spots of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, and parC and inactivated the efflux regulator genes so as to overexpress the corresponding multidrug resistance (MDR) efflux pumps. We then introduced the respective mutations into the reference strain PA14 singly and in various combinations. Whereas the combined inactivation of two efflux regulator-encoding genes did not lead to resistance levels higher than those obtained by inactivation of only one efflux regulator-encoding gene, the combination of mutations leading to increased efflux and target alteration clearly exhibited an additive effect. This combination of target alteration and overexpression of efflux pumps was commonly observed in clinical P. aeruginosa isolates; however, these two mechanisms were frequently found not to be sufficient to explain the level of fluoroquinolone resistance. Our results suggest that there are additional mechanisms, independent of the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and/or MexXY-OprM efflux pump, that increase ciprofloxacin resistance in isolates with mutations in the QRDRs.
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