Interspecific interactions infections select against Pseudomonas aeruginosa mutators, analysis of clinical samples

This study refers to analysis of isolates derived from Pseudomonas aeruginosa infections of cystic fibrosis patients:Bacteria with elevated mutation rates (mutators) are associated with treatment failure in chronic respiratory infections. We show that mutation frequency in the opportunistic pathogen Pseudomonas aeruginosa is negatively correlated with the frequency and diversity of co-infecting bacteria in chronic lung infections of cystic fibrosis (CF) patients. We experimentally demonstrate in vitro 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 were deleterious in their presence. 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.