Co-occurring microflora and mucin drive Pseudomonas aeruginosa diversification and pathoadaptation.

While several environmental factors contribute to the evolutionary diversification of the pathogenic bacterium Pseudomonas aeruginosa during cystic fibrosis lung infections, relatively little is known about the impact of the surrounding microbiota. By using in vitro experimental evolution, we show that the presence of Stenotrophomonas maltophilia, Staphylococcus aureus, or them both, prevent the evolution of loss of virulence, which repeatedly occurs in the absence of these species due to mutations in regulators of the Pseudomonas Quinolone Signal quorum sensing system, vqsM and pqsR. Moreover, the strength of the effect of co-occurring species is attenuated through changes in the physical environment by the addition of mucin, resulting in selection for phenotypes resembling those evolved in the absence of the co-occurring species. Together, our findings show that variation in mucosal environment and the surrounding polymicrobial environment can determine the evolutionary trajectory of P. aeruginosa, partly explaining its diversification and pathoadaptation from acute to chronic phenotype during cystic fibrosis lung infections.