The efficacy of antibiotic treatments targeting polymicrobial communities is not well predicted by conventional in vitro susceptibility testing based on determining minimum inhibitory concentration (MIC) in monocultures. One reason for this is that inter-species interactions can alter the community members’ susceptibility to antibiotics. Here we quantify, and identify mechanisms for, community-modulated changes of efficacy for clinically relevant antibiotics against the pathogen Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities derived from clinical samples. We demonstrate that multi-drug resistant Stenotrophomonas maltophilia can provide high levels of antibiotic protection to otherwise sensitive P. aeruginosa. Exposure protection to imipenem was provided by chromosomally encoded metallo-β-lactamase that detoxified the environment; protection was dependent upon S. maltophilia cell density and was provided by S. maltophilia strains isolated from CF sputum, increasing the MIC of P. aeruginosa by up to 16-fold. In contrast, the presence of S. maltophilia provided no protection against meropenem, another routinely used carbapenem. Mathematical ordinary differential equation modelling shows that the level of exposure protection provided against different carbapenems can be explained by differences in antibiotic efficacy and inactivation rate. Together, these findings reveal that exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have large impacts on pathogen antibiotic susceptibility, highlighting the importance of microbial ecology for designing successful antibiotic treatments for multispecies communities.

基于确定单一培养物中的最小抑菌浓度 (MIC) 的常规体外药敏试验无法很好地预测针对多种微生物群落的抗生素治疗的疗效。原因之一是物种间的相互作用可以改变社区成员对抗生素的敏感性。在这里，我们量化并确定了临床相关抗生素对来自临床样本的模型囊性纤维化 (CF) 肺群落中的病原体铜绿假单胞菌的疗效变化的群落调节机制。我们证明了多重耐药性嗜麦芽窄食单胞菌可以为其他敏感的铜绿假单胞菌提供高水平的抗生素保护. 亚胺培南的暴露保护是由染色体编码的金属-β-内酰胺酶提供的，它可以使环境解毒；保护取决于S. maltophilia细胞密度，并由从 CF 痰中分离的S. maltophilia菌株提供，使铜绿假单胞菌的 MIC 增加多达 16 倍。相反，S. maltophilia的存在对另一种常用的碳青霉烯类美罗培南没有提供保护作用。数学常微分方程模型表明，针对不同碳青霉烯类的暴露保护水平可以用抗生素疗效和灭活率的差异来解释。总之，这些发现表明，利用预先发生的抗菌素耐药性和种间竞争，可以对病原体抗生素敏感性产生重大影响，突出了微生物生态学对于为多物种群落设计成功的抗生素治疗的重要性。