Genomic evolution of Pseudomonas aeruginosa mutator populations in cystic fibrosis chronic airway infections

FELIZIANI S; MARVIG R; LUJÁN AM; MOYANO AJ; URRETA VIZCAYA M; MOLIN S; SMANIA AM

Puerto Varas

Congreso; XII PABMB Congress; 2013

Panamerican Association for Biochemistry and Molecular Biology

Hypermutability due to deficiency in the DNA mismatch repair system (MRS) is highly selected in P. aeruginosa (PA) chronic airway infection (CAI) in cystic fibrosis (CF) patients and it may be an adaptive strategy used by PA for diversification and persistence. However, to date the evolution and dynamics of PA mutators has not been explored at a population level. This work studied the impact of hypermutability on PA genome diversity during its evolution in CAI. Whole genome sequencing was conducted in cross-sectional and longitudinal analyses of 27 isolates from 2 CF patients infected by distinct PA clones. We found that once emerged, MRS-mutator isolates reach high frequencies and dominate the population. Phylogenetic analysis revealed high diversity among contemporary clones due to a high accumulation of mutations skewed towards transitions and towards small indels in simple sequence repeats (SSR). Moreover, we established that SSR together with MRS deficiency can bias mutagenic pathways during CAI. Notably, a mutS-carrying-mutation subpopulation showed low mutation frequency evidencing a reversion phenomenon. This is the first recording of such phenomenon in CAI. Even though the evolution of mutators in CAI was marked by negative selection and genetic drift, evidence of parallel evolution in pathoadaptive genes, resulting in the alteration of antibiotic resistance, virulence, motility and attachment functions, was observed.