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.

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孔蛋白基因。虽然单一培养和共培养处理之间的耐药水平没有差异，但嗜麦芽糖链球菌的存在增加了 4 μg/ml 亚胺培南浓度下亚胺培南耐药性演变的速率。出乎意料的是，亚胺培南耐药性的演变与嗜麦芽糖链球菌的灭绝同时发生，因为绿脓素的产量增加，对嗜麦芽糖链球菌具有细胞毒性。总之，我们的结果表明，由于保护物种的竞争排斥，病原体抗性进化可以破坏抗生素暴露保护。这种生态进化反馈可能有助于解释 CF 群落内细菌物种相对丰度的变化，尽管对抗假单胞菌药物具有内在抗性。