Adaptation of Pseudomonas aeruginosa to repeated invasion into a commensal competitor

Abstract

The host-associated microbiome is an important barrier to bacterial pathogen colonization and can mediate protection through a variety of mechanisms. We wanted to investigate the potential consequences of selection imposed by commensal bacterial competitors on an invading bacterial pathogen. To do this, we tested the ability of the opportunistic pathogen Pseudomonas aeruginosa to invade pre-established communities of an abundant commensal bacterium in the human microbiome, Staphylococcus epidermidis. We passaged ten independent lines of P. aeruginosa through daily invasion into a pre-established S. epidermidis population (coculture evolved lines), alongside daily passage through monoculture conditions (monoculture evolved lines). The monoculture evolved lines showed strong parallel evolution in the Wsp (Wrinkly spreader phenotype) signal transducing system involved in biofilm formation, and significantly elevated biofilm formation. On the other hand, adaptation to S. epidermidis occurred via mutations in a diverse set of genes, and the coculture evolved lines showed much weaker evidence for parallel evolution, suggesting that the selective pressure imposed by competition with S. epidermidis is more complex than the pressure imposed by culture conditions. Interestingly, the elevated biofilm formation phenotype seen in the monoculture evolved lines was not observed in the lines evolved in the presence of S. epidermidis, raising the question of whether enhanced biofilm formation did not evolve with S. epidermidis present because it was not beneficial, or because S. epidermidis may be able to restrict this evolutionary path by inhibiting biofilm formation.