Coexistence and Within-Host Evolution of Diversified Lineages of Hypermutable in Long-term Cystic Fibrosis Infections

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Patients with cystic fibrosis (CF) are often colonized by a single clone of the common, widespread bacterium Pseudomonas aeruginosa, resulting in chronic airway infections. Long-term persistence of the bacteria involves the emergence and selection of multiple phenotypic variants. Among these are “mutator” variants characterized by increased mutation rates resulting from the inactivation of DNA repair systems. The genetic evolution of mutators during the course of chronic infection is poorly understood, and the effects of hypermutability on bacterial population structure have not been studied using genomic approaches. We evaluated the genomic changes undergone by mutator populations of P. aeruginosa obtained from single sputum samples from two chronically infected CF patients, and found that mutators completely dominated the infecting population in both patients. These populations displayed high genomic diversity based on vast accumulation of stochastic mutations. Our results are in contrast to the concept of a homogeneous population consisting of a single dominant clone; rather, they support a model of populations structured by diverse subpopulations that coexist within the patient. Certain genes involved in adaptation were highly and convergently mutated in both lineages, suggesting that these genes were beneficial and potentially responsible for the co-selection of mutator alleles.

Vyšlo v časopise: Coexistence and Within-Host Evolution of Diversified Lineages of Hypermutable in Long-term Cystic Fibrosis Infections. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004651
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004651

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