Resistance evolution can disrupt antibiotic exposure protection through competitive exclusion of the protective species

Abstract

Antibiotic degrading bacteria 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 pathogen antibiotic resistance evolution. Here, we utilised a two-species model cystic fibrosis (CF) community where we evolved the bacterial pathogen Pseudomonas aeruginosa in a range of imipenem concentrations in the absence or presence of Stenotrophomonas maltophilia, which can detoxify the environment by hydrolysing β-lactam antibiotics. We found that P. aeruginosa quickly evolved resistance to imipenem via parallel loss of function mutations in the oprD porin gene. While the level of resistance did not differ between mono- and co-culture treatments, the presence of S. maltophilia increased the rate of imipenem resistance evolution in the four μg/ml imipenem concentration. Unexpectedly, imipenem resistance evolution coincided with the extinction of S. maltophilia due to increased production of pyocyanin, which was cytotoxic to S. maltophilia. Together, our results show that pathogen resistance evolution can disrupt antibiotic exposure protection due to competitive exclusion of the protective species. Such eco-evolutionary feedbacks may help explain changes in the relative abundance of bacterial species within CF communities despite intrinsic resistance to anti-pseudomonal drugs.