Impact of Mismatch Repair System (MRS) deficiency on the evolution of Pseudomonas aeruginosa

SOFÍA FELIZIANI; SOEREN MOLIN; ANDREA M. SMANIA

Potrero de los Funes, San Luis

Congreso; XLVII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Cystic fibrosis (CF) patients acquire P. aeruginosa (PA) during early childhood later on developing chronic airway infections (CAI) established by a same bacterial lineage, which persists through their entire life by using various adaptive mechanisms. Among them, PA suffers phenotypic diversification based on mutagenic events, leading to the emergence of adaptive variants such as mucoids, sessile and avirulents.  Mutators, mainly due to MRS deficiency, are also highly prevalent in CAI and have been associated with increased antibiotic resistance. However, their role remains to be completely elucidated. This work aims to study the impact of hypermutability on PA phenotypic and genetic diversification through many generations of persistence in CF patients. We set up longitudinal (20 years) and cross-sectional (90 isolates) collections of isolates from CF patients harboring mutator strains, which are being analyzed by using a combination of whole genome sequencing, BIOLOG metabolic profiling and phenotypic characterization. Results to date on metabolic and phenotypic diversity indicate that mutator and nonmutator clones follow convergent evolution into the same adaptive traits. Notably, mutators with different MRS mutations can be observed into a single patient, even coexisting at the same time, confirming strong selective pressures for mutators in the harsh CF lung environment.