ArticleAntimicrobial agents and chemotherapy2005
Hypermutation is a key factor in development of multiple-antimicrobial resistance in Pseudomonas aeruginosa strains causing chronic lung infections.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.
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135 citing papers in PubMed, 1 synthesis or guideline pooled it, 310 citations in OpenAlex.
- The Status of Carbapenem Resistance in Cystic Fibrosis: A Systematic Review and Meta-Analysis.The Yale journal of biology and medicine · 2022Pooled it
- Comparative study of antibiotic resistance and virulence profiles of exoU and exoS Pseudomonas aeruginosa isolates from urinary tract infections and microbial keratitis in Bangladesh and India.World journal of microbiology & biotechnology · 2026Article
- New Cross-Linked Polymeric Materials Modified with Antimicrobial Compounds in Relation to Their Biological Activities and Biodegradation by the Laccase-Producing FungusBiomolecules · 2026Article
- The role of environmental stress in promoting mutators through evolutionary rescue: quantitative predictions.Genetics · 2025Article
- Effect of Mutations on the Evolution of Extended Spectrum β-lactamases (ESBL).The protein journal · 2025Review
- Differences in antimicrobial resistance between exoU and exoS isolates of Pseudomonas aeruginosa.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Immune system dynamics in response to Pseudomonas aeruginosa biofilms.NPJ biofilms and microbiomes · 2025Review
- Co-culture biofilm patterns among different Pseudomonas aeruginosa clones from cystic fibrosis patients.Biofilm · 2025Article
- Transcriptional diversification in a human-adapting zoonotic pathogen drives niche-specific evolution.Nature communications · 2025Article
- Mutational signature analysis predicts bacterial hypermutation and multidrug resistance.Nature communications · 2025Article
- Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance.Nature reviews. Microbiology · 2024Review
- The role of hypermutation and collateral sensitivity in antimicrobial resistance diversity ofmBio · 2024Article
- Dissemination of mcr-1 and β-lactamase genes among Pseudomonas aeruginosa: molecular characterization of MDR strains in broiler chicks and dead-in-shell chicks infections.Annals of clinical microbiology and antimicrobials · 2024Article
- Phenotypes of amSystems · 2024Article
- Evolvability: filling the explanatory gap between adaptedness and the long-term mathematical conception of fitness.Biology & philosophy · 2024Article
- Review
- Mechanisms of antibiotic resistance inBiofilm · 2023Article
- Spatial heterogeneity in biofilm metabolism elicited by local control of phenazine methylation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Epidemiological and Genetic Characteristics of Clinical Carbapenem-ResistantMicrobiology spectrum · 2023Article
- Mutators can drive the evolution of multi-resistance to antibiotics.PLoS genetics · 2023Article
75 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Pseudomonas aeruginosa is the most relevant pathogen producing chronic lung infections in patients with chronic underlying diseases such as cystic fibrosis (CF), bronchiectasis, and chronic obstructive pulmonary disease (COPD). Hypermutable (or mutator) P. aeruginosa strains, characterized by increased (up to 1,000-fold) spontaneous mutation rates due to alterations of the DNA mismatch repair (MMR) system have been found at high frequencies in the lungs of CF patients, but their role in other chronic processes is still unknown. Sixty-two P. aeruginosa isolates from 30 patients with underlying non-CF chronic respiratory diseases (22 with bronchiectasis and 8 with COPD) and documented chronic infection were studied. Antibiotic susceptibility profiles and mutation frequencies were determined, and complementation assays using the cloned wild-type mutS gene and molecular epidemiology studies (pulsed-field electrophoresis, [PFGE]) were performed with these strains. Thirty-three (53%) of the isolates were hypermutable, and 17 (57%) of the 30 patients were colonized by hypermutable strains. Strains from 11 of the 17 patients were found to be defective in the MMR mutS gene by complementation assays. Interpatient transmission of strains was ruled out by PFGE. Multiple-antimicrobial resistance was documented in 42% of the hypermutable strains in contrast to 0% resistance in the nonhypermutable strains (P < 0.0001). Hypermutable P. aeruginosa strains are extremely prevalent in chronic infections in contrast to what has been described in acute processes, suggesting a role of hypermutation in bacterial adaptation for long-term persistence. Furthermore, hypermutation is found to be a key factor for the development of multiple-antimicrobial resistance, and therefore these findings are expected to have important consequences for the treatment of chronic infections.
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