Quorum Sensing mediated tradeoff limits mutators fixation during ploymicrobial infections?

LUJAN AM; SOMMER LM; MARVIG R; CIOFU O; SMANIA AM; KROGH JOHANSEN H; MOLIN S; BUCKLING A

Salta

Congreso; LV Annual SAIB, LIV PABMB 2019; 2019

Bacteria with elevated mutations rates (mutators) can reach high frequencies in cystic fibrosis (CF) chronic infections and are associated with treatment failure in chronic respiratory infections. The causes and consequences of bacterial elevated mutation rates have been widely studied and results suggest that mutators might be selected because their higher probability of generating beneficial mutations. However, it is notable that there are large between-patient differences in mutator frequency; even where the age and treatment protocols of patients are similar.Understanding this variation may provide opportunities for interventions that could minimize mutator evolution and the severity of infections.Possible drivers of variation in mutator frequencies are interactions with other bacterial co-infecting bacterial species. Ecological and evolutionary changes in populations of co-occurring species may result in continually changing selection pressures, potentially selecting for mutators. Alternatively, mutators may be selected against if competitors constrain adaptation to other components of the environment. Here, we used a combination of correlational in vivo data and in vitro experiments to determine the role played by co-occurring pathogens in driving variation in Pseudomonas aeruginosa mutation rate in chronic infections. By performing metagenomic analysis of CF sputum samples we show that mutation frequency in P. aeruginosa is negatively correlated with the frequency and diversity of co-infecting bacteria in chronic lung infections of CF patients. By competing in vitro P. aeruginosa mutators against wild-type in the presence and in the absence of the bacterial community we demonstrate that mutators have a fitness advantage in the absence of other CF-associated species, and that this was in part because mutations in the main Quorum-Sensing (QS) regulators that were beneficial in the absence of competitors but deleterious in theirpresence. These QS genes were also more likely to be mutated in P. aeruginosa CF populations showing elevated mutations frequencies in vivo.Our results demonstrate that interspecific competition constrains the evolution of mutation rates, and more generally highlights the crucial role of the community context in microbial evolution and virulence.