Normal mutation rate variants arise in mutator Pseudomonas aeruginosa chronic infection populations

FELIZIANI S; SMANIA AM

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Moleculari; 2014

Hypermutability due to DNA mismatch repair system (MRS) deficiency is a common trait evolved by Pseudomonas aeruginosa (PA) strains in cystic fibrosis (CF) chronic infections. We have previously investigated the long-term evolution of mutators in CF airways by sequencing 27 genomes of PA from two CF patients (CFA and CFD) infected by single clones. Comparison of the genomes of 11 isolates obtained from single-time point samples showed extensive within-patient genomic diversification; the populations were composed of different sub-lineages that had coexisted for many years since the initial colonization of the patient. Despite of harboring MRS loss-of-function mutations, a small percentage (6%) of the CFD population showed a reduced mutation frequency similar to that of normo-mutable strains. Our sequencing data suggested that the most feasible explanation is the emergence of secondary mutations, in no MRS genes, that compensate for hypermutability, since neither reversion of the original mutation nor duplication of MRS genes were observed in the normo-mutable genomes. Within 112 analyzed genes, which are involved in replication, recombination, DNA repair adaptation, oxidative stress, and SOS response, only 8 were differentially mutated in the normo-mutable isolates. There are no previous studies about a possible compensation for MRS deficiency due to the observed mutations.