ArticleAntimicrobial agents and chemotherapy2006
Involvement of the MexXY-OprM efflux system in emergence of cefepime resistance in clinical strains of Pseudomonas aeruginosa.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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68 citing papers in PubMed, 137 citations in OpenAlex.
- Cefepime and New Cefepime/Beta-Lactamase Inhibitor Combination for the Treatment of Gram-Negative Bacteria: Chemical Structure and Mechanism of Action, Microbiological Target, Clinical Use and PK/PD Characteristics.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Antimicrobial Resistance Trends, Resistance Mechanisms, and Antibiotic Consumption in COVID-19 Versus Non-COVID-19 Units: A Seven-Year Retrospective Cohort Study.Antibiotics (Basel, Switzerland) · 2025Article
- Structure and mechanism of taniborbactam inhibition of the cefepime-hydrolyzing, partial R2-loop deletionAntimicrobial agents and chemotherapy · 2025Article
- Loss of OprD function is sufficient for carbapenem-resistance-only but insufficient for multidrug resistance in Pseudomonas aeruginosa.BMC microbiology · 2025Article
- Antibiotic Resistance and Virulence Determinants ofMicroorganisms · 2025Article
- Involvement of theFrontiers in cellular and infection microbiology · 2025Article
- Effects of quorum sensing-interfering agents, including macrolides and furanone C-30, and an efflux pump inhibitor on nitrosative stress sensitivity inMicrobiology (Reading, England) · 2024Article
- Potentiation of Antibiotic Activity of Aztreonam against Metallo-β-Lactamase-Producing Multidrug-ResistantPharmaceutics · 2024Article
- Using phage to drive selections toward restoring antibiotic sensitivity inFrontiers in microbiology · 2024Article
- Mechanisms of Antibiotic and Biocide Resistance That Contribute toBiomedicines · 2023Review
- PBP Target Profiling by β-Lactam and β-Lactamase Inhibitors in Intact Pseudomonas aeruginosa: Effects of the Intrinsic and Acquired Resistance Determinants on the Periplasmic Drug Availability.Microbiology spectrum · 2023Article
- Exposure ofAntibiotics (Basel, Switzerland) · 2022Article
- The MexJK Multidrug Efflux Pump Is Not Involved in Acquired or Intrinsic Antibiotic Resistance inInternational journal of molecular sciences · 2022Article
- New Drugs for the Treatment ofAntibiotics (Basel, Switzerland) · 2022Review
- Incidence and Molecular Characterization of Carbapenemase Genes in Association with Multidrug-Resistant Clinical Isolates of Pseudomonas aeruginosa from Tertiary Healthcare Facilities in Southwest Nigeria.Current microbiology · 2021Article
- Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2021Review
- The rise and the fall of aMicrobial genomics · 2021Article
- Role of RND Efflux Pumps in Drug Resistance of Cystic Fibrosis Pathogens.Antibiotics (Basel, Switzerland) · 2021Review
- The Building Blocks of Antimicrobial Resistance inFrontiers in cellular and infection microbiology · 2021Review
- Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cefepime (FEP) and ceftazidime (CAZ) are potent beta-lactam antibiotics with similar MICs (1 to 2 mug/ml) for wild-type strains of Pseudomonas aeruginosa. However, recent epidemiological studies have highlighted the occurrence of isolates more resistant to FEP than to CAZ (FEPr/CAZs profile). We thus investigated the mechanisms conferring such a phenotype in 38 clonally unrelated strains collected in two French teaching hospitals. Most of the bacteria (n=32; 84%) appeared to stably overexpress the mexY gene, which codes for the RND transporter of the multidrug efflux system MexXY-OprM. MexXY up-regulation was the sole FEP resistance mechanism identified (n=12) or was associated with increased levels of pump MexAB-OprM (n=5) or MexJK (n=2), synthesis of secondary beta-lactamase PSE-1 (n=10), derepression of cephalosporinase AmpC (n=1), coexpression of both OXA-35 and MexJK (n=1), or production of both PSE-1 and MexAB-OprM (n=1). Down-regulation of the mexXY operon in seven selected strains by the plasmid-borne repressor gene mexZ decreased FEP resistance from two- to eightfold, thereby demonstrating the significant contribution of MexXY-OprM to the FEPr/CAZs phenotype. The six isolates of this series that exhibited wild-type levels of the mexY gene were found to produce beta-lactamase PSE-1 (n=1), OXA-35 (n=4), or both PSE-1 and OXA-35 (n=1). Altogether, these data provide evidence that MexXY-OprM plays a major role in the development of FEP resistance among clinical strains of P. aeruginosa.
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