ArticleAntimicrobial agents and chemotherapy2014
Multiple mutations lead to MexXY-OprM-dependent aminoglycoside resistance in clinical strains of Pseudomonas aeruginosa.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 108 citations in OpenAlex.
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- Within-patient gene transfer between transiently and chronically infecting bacteria causes extreme antibiotic resistance during lung infections.Nature microbiology · 2026Article
- MexXY-OprM efflux pump mediates resistance to odilorhabdins inMicrobiology spectrum · 2026Article
- Broadly Defined Antibiotic Adjuvants forThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026Review
- Quorum sensing regulation by the nitrogen phosphotransferase system inJournal of bacteriology · 2025Article
- Regulation, structure, and activity of theAntimicrobial agents and chemotherapy · 2025Review
- Anaerobiosis and Mutations Can Reduce Susceptibility ofPathogens (Basel, Switzerland) · 2025Article
- Common regulatory mutation increases single-cell survival to antibiotic exposures inbioRxiv : the preprint server for biology · 2024Article
- Keeping up with the pathogens: improved antimicrobial resistance detection and prediction from Pseudomonas aeruginosa genomes.Genome medicine · 2024Article
- Antibiotic influx and efflux in Pseudomonas aeruginosa: Regulation and therapeutic implications.Microbial biotechnology · 2024Review
- Article
- Genetic and Phenotypic Analysis of Phage-Resistant Mutant Fitness Triggered by Phage-Host Interactions.International journal of molecular sciences · 2023Article
- Age of Antibiotic Resistance in MDR/XDR Clinical Pathogen ofPharmaceuticals (Basel, Switzerland) · 2023Review
- The Art of War withAntibiotics (Basel, Switzerland) · 2023Review
- An Amino Acid Substitution in Elongation Factor EF-G1A Alters the Antibiotic Susceptibility of Pseudomonas aeruginosa LasR-Null Mutants.Journal of bacteriology · 2023Article
- Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital.Microbiology spectrum · 2023Article
- Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa.Scientific reports · 2023Article
- Mechanisms of Antibiotic and Biocide Resistance That Contribute toBiomedicines · 2023Review
- Role of Efflux Pumps on Antimicrobial Resistance inInternational journal of molecular sciences · 2022Review
- The Association between Biofilm Formation and Antimicrobial Resistance with Possible Ingenious Bio-Remedial Approaches.Antibiotics (Basel, Switzerland) · 2022Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Constitutive overproduction of the pump MexXY-OprM is recognized as a major cause of resistance to aminoglycosides, fluoroquinolones, and zwitterionic cephalosporins in Pseudomonas aeruginosa. In this study, 57 clonally unrelated strains recovered from non-cystic fibrosis patients were analyzed to characterize the mutations resulting in upregulation of the mexXY operon. Forty-four (77.2%) of the strains, classified as agrZ mutants were found to harbor mutations inactivating the local repressor gene (mexZ) of the mexXY operon (n = 33; 57.9%) or introducing amino acid substitutions in its product, MexZ (n = 11; 19.3%). These sequence variations, which mapped in the dimerization domain, the DNA binding domain, or the rest of the MexZ structure, mostly affected amino acid positions conserved in TetR-like regulators. The 13 remaining MexXY-OprM strains (22.8%) contained intact mexZ genes encoding wild-type MexZ proteins. Eight (14.0%) of these isolates, classified as agrW1 mutants, overexpressed the gene PA5471, which codes for the MexZ antirepressor ArmZ [corrected], with 5 strains exhibiting growth defects at 37°C and 44°C, consistent with mutations impairing ribosome activity. Interestingly, one agrW1 mutant appeared to harbor a 7-bp deletion in the coding sequence of the leader peptide, PA5471.1, involved in ribosome-dependent, translational attenuation of PA5471 expression. Finally, DNA sequencing and complementation experiments revealed that 5 (8.8%) strains, classified as agrW2 mutants, harbored single amino acid variations in the sensor histidine kinase of ParRS, a two-component system known to positively control mexXY expression. Collectively, these results demonstrate that clinical strains of P. aeruginosa exploit different regulatory circuitries to mutationally overproduce the MexXY-OprM pump and become multidrug resistant, which accounts for the high prevalence of MexXY-OprM mutants in the clinical setting.
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