title: Parallel evolution and local differentiation in quinolone resistance in Pseudomonas aeruginosa.
abstract: The emergence and spread of antibiotic resistance in pathogens is a major impediment to the control of microbial disease. Here, we review mechanisms of quinolone resistance in Pseudomonas aeruginosa, an important nosocomial pathogen and a major cause of morbidity in cystic fibrosis (CF) patients. In this quantitative literature review, we find that mutations in DNA gyrase A, the primary target of quinolones in Gram-negative bacteria, are the most common resistance mutations identified in clinical samples of all origins, in keeping with previous observations. However, the identities of non-gyrase resistance mutations vary systematically between samples isolated from CF patients and those isolated from acute infections. CF-derived strains tend to harbour mutations in the efflux pump regulator nfxB, while non-CF strains tend to bear mutations in the efflux regulator mexR or in parC, which encodes one of two subunits of DNA topoisomerase IV. We suggest that differences in resistance mechanisms between CF and non-CF strains result either from local adaptation to different sites of infection or from differences in mutational processes between different environments. We further discuss the therapeutic implications of local differentiation in resistance mechanisms to a common antibiotic.
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Wong
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Rees
authors.initials: R
authors.lastname: Kassen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D003550:Cystic Fibrosis / Q000150:complications; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial; D019143:Evolution, Molecular; D006801:Humans; D020125:Mutation, Missense; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015363:Quinolones / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C423620:MexR protein, Pseudomonas aeruginosa; C077901:NfxB protein, Pseudomonas aeruginosa; D015363:Quinolones; D012097:Repressor Proteins; D014157:Transcription Factors; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase