Resistance evolution can disrupt antibiotic exposure protection through competitive exclusion of the protective species data-sets.xlsx

Bacterial community members that degrade antibiotics can reduce the efficacy of drug treatments by providing antibiotic exposure protection to pathogens. While this has been demonstrated at the ecological timescale, it is unclear how exposure protection might alter and be affected by antibiotic resistance evolution. Here, we utilised a two-species model Cystic Fibrosis (CF) community where the bacterial pathogen <i>Pseudomonas aeruginosa</i> was experimentally evolved in a range of imipenem concentrations in the absence or presence of <i>Stenotrophomonas maltophilia, </i>a multidrug resistant pathogen which can degrade β-lactam antibiotics, detoxifying the growth environment. We found that <i>P. aeruginosa</i> evolved resistance to imipenem at all concentrations above the minimum inhibitory concentration. While the level of resistance did not differ between mono- and co-culture treatments, the presence of <i>S. maltophilia</i> increased the rate of imipenem resistance evolution, which was linked to parallel loss of function mutations in the <i>oprD</i> porin gene. Unexpectedly, the evolution of imipenem resistance led to the extinction of <i>S. maltophilia,</i> which otherwise persisted in co-cultures in the absence of imipenem. This could be explained by increased production of pyocyanin by imipenem resistant <i>P. aeruginosa</i> strains, which was cytotoxic to <i>S. maltophilia</i>. Together, our results show that pathogen resistance evolution can disrupt antibiotic exposure protection due to competitive exclusion of the protective species, potentially triggering eco-evolutionary feedbacks and succession of resistant bacterial species in polymicrobial CF communities.