title: Hypermutability in environmental Pseudomonas aeruginosa and in populations causing pulmonary infection in individuals with cystic fibrosis.
abstract: Pseudomonas aeruginosa is the pathogen most commonly associated with morbidity and mortality in cystic fibrosis (CF) patients. The host-pathogen interactions responsible for progressive CF lung diseases are complex. However, there is growing interest in the role of hypermutable P. aeruginosa (that is, those strains with an increased mutation frequency due to mutations in mismatch repair and error prevention genes), in terms of both bacterial adaptation and antimicrobial resistance. The prevalence of hypermutable P. aeruginosa in chronic CF infection has been established, and at 37 % is surprisingly high. To the authors' knowledge, there are no reports of prevalence during the early stages of infection, in environmental pseudomonas, which are believed to be the primary source of infection, and in epidemic strains, which have emerged as a major challenge. The aim of this study was to establish the prevalence of hypermutable P. aeruginosa in these pseudomonas populations. The hypothesis was that hypermutability would be rare in early and in environmental P. aeruginosa but in contrast would explain the relatively recent emergence of epidemic strains. It was found that 10/100 (10 %) of early isolates were strong or weak mutators, suggesting that the CF lung is not the only factor influencing the existence of mutators in this group of patients. Two weak mutators (6 %) were found in 32 environmental isolates. Only two of 15 (13 %) epidemic P. aeruginosa strains were hypermutable, and although closer analysis revealed this issue to be complex, on the whole the data suggested that the atypical characteristics of these highly transmissible strains cannot solely be explained by this phenomenon. The higher than predicted prevalence of mutators in early infection, and in environmental isolates, reinforces the importance of early and aggressive treatment for P. aeruginosa infection in CF.
authors.affiliation: Cystic Fibrosis Group, Centre for Infectious Diseases, University of Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Dervla T
authors.initials: DT
authors.lastname: Kenna
authors.affiliation: Cystic Fibrosis Group, Centre for Infectious Diseases, University of Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Doherty
authors.affiliation: Department of Microbiology, Papworth Hospital NHS Trust, Papworth Everard, Cambridge CB3 8RE, UK.
authors.forename: Juliet
authors.initials: J
authors.lastname: Foweraker
authors.affiliation: The Whitchurch Laboratory, Department of Microbiology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria 3800, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Macaskill
authors.affiliation: Cystic Fibrosis Group, Centre for Infectious Diseases, University of Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Barcus
authors.affiliation: Cystic Fibrosis Group, Centre for Infectious Diseases, University of Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: John R W
authors.initials: JRW
authors.lastname: Govan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D045643:DNA Repair Enzymes / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004783:Environmental Microbiology; D005798:Genes, Bacterial; D006801:Humans; D009154:Mutation / Q000502:physiology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D017422:Sequence Analysis, DNA
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D045643:DNA Repair Enzymes