?Evolution of Pseudomonas aeruginosa mismatch repair system mutators in a community context

LUJAN, ADELA M; MADSEN, LEA; MARVIG, RASMUS; SHARMA, MD; KROGH JEHASEN HELLE; MOLIN, SOEREN; BUCKLING, ANGUS

Cambridge

Workshop; Understanding Microbial Communities; Function, Structure and Dynamics; 2014

Isaac Newton Institute for mathematical Sciences

Under changing environmental conditions such as chronic infectious processes, an increase in the mutation rate could confer a selective advantage. Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections in patients with cystic fibrosis (CF). A striking feature of these infections is the very high prevalence (30?60%) of mutator strains, mainly due to alterations in Mismatch Repair System (MRS). Theoretical and experimental approaches have attempted to explain the selection of MRS-mutators as the result of co-selection (hitchhiking) with linked beneficial mutations such as those conferring antibiotic resistance. However, most of the studies these promising studies are base in pure test-tube experiments and bacteria do not exist as isolated pure cultures in nature and thus limit their extrapolation. Moreover, CF chronic infections are polymicrobial infections whereby different bacterial species can interact and influence each other. Here, we investigate for the first time how the evolution of P. aeruginosa mutation rates is affected by the natural microbial community in a CF context. To do this we carried out two complementary approaches. First, we determined the correlation between the mutation frequency of P. aeruginosa and the bacterial community diversity in CF sputum samples. In addition, by growing P. aeruginosa wild-type and mutator strains in artificial CF communities we investigated the impact of the presence of other co-infecting bacteria in P. aeruginosa mutator evolution and fitness.