title: High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection.
abstract: The lungs of cystic fibrosis (CF) patients are chronically infected for years by one or a few lineages of Pseudomonas aeruginosa. These bacterial populations adapt to the highly compartmentalized and anatomically deteriorating lung environment of CF patients, as well as to the challenges of the immune defenses and antibiotic therapy. These selective conditions are precisely those that recent theoretical studies predict for the evolution of mechanisms that augment the rate of variation. Determination of spontaneous mutation rates in 128 P. aeruginosa isolates from 30 CF patients revealed that 36% of the patients were colonized by a hypermutable (mutator) strain that persisted for years in most patients. Mutator strains were not found in 75 non-CF patients acutely infected with P. aeruginosa. This investigation also reveals a link between high mutation rates in vivo and the evolution of antibiotic resistance.
authors.affiliation: Department of Microbiology and Unit for Cystic Fibrosis, Hospital Ramón y Cajal, National Institute of Health (INSALUD), 28034 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Oliver
authors.forename: R
authors.initials: R
authors.lastname: Cantón
authors.forename: P
authors.initials: P
authors.lastname: Campo
authors.forename: F
authors.initials: F
authors.lastname: Baquero
authors.forename: J
authors.initials: J
authors.lastname: Blázquez
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics* / Q000528:radiation effects; D001980:Bronchi / Q000382:microbiology / Q000473:pathology; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000235:genetics / Q000382:microbiology*; D004352:Drug Resistance, Microbial; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011552:Pseudomonas Infections / Q000453:epidemiology / Q000235:genetics / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000528:radiation effects; D019105:Random Amplified Polymorphic DNA Technique; D013030:Spain / Q000453:epidemiology