1887

Abstract

The high prevalence of hypermutable (mismatch repair-deficient) strains in patients with cystic fibrosis (CF) is thought to be driven by their co-selection with adaptive mutations required for long-term persistence. Whether the increased mutation rate of naturally hypermutable strains is associated with a biological benefit or cost for the colonization of secondary environments is not known. Thirty-nine strains were collected from ten patients with CF during their course of chronic lung infections and screened for hypermutability. Seven hypermutable strains (18 %) isolated from six patients with CF (60 %) were identified and assigned to five different genotypes. Complementation and sequence analysis in the , and genes of these hypermutable strains revealed novel mutations. To understand the consequences of hypermutation for the fitness of the organisms, five pairs of clinical wild-type/hypermutable, clonally related strains and the laboratory strains PAO1/PAO1Δ were subjected to competition and in the agar-beads mouse model of chronic airway infection. When tested in competition assay , the wild-type outcompeted four clinical hypermutable strains and the PAO1Δ strain. , all of the hypermutable strains were less efficient at establishing lung infection than their wild-type clones. These results suggest that hypermutation is associated with a biological cost, reducing the potential for colonization of new environments and therefore strain transmissibility.

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2007-05-01
2021-06-18
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