Inter-species interactions alter antibiotic efficacy in bacterial communities

• Published in: The ISME Journal 2022-03, Vol.16 (3), p.812-821
• Main Authors: Bottery, Michael J., Matthews, Jessica L., Wood, A. Jamie, Johansen, Helle Krogh, Pitchford, Jon W., Friman, Ville-Petri
• Format: Article
• Language: English
• Subjects: 45/23; 631/158/855; 631/326/22/1290; 692/699/255/1318; 82/58; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial resistance; beta-Lactamases - genetics; Biomedical and Life Sciences; Carbapenems; Cell density; Community; Cystic fibrosis; Cystic Fibrosis - microbiology; Differential equations; Drug resistance; Ecology; Evolutionary Biology; Humans; Imipenem; Inactivation; Life Sciences; Mathematical models; Meropenem; Metallo-β-lactamase; Metallography; Microbial Ecology; Microbial Genetics and Genomics; Microbial Sensitivity Tests; Microbiology; Microorganisms; Minimum inhibitory concentration; Monoculture; Multidrug resistance; Pathogens; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Sputum; β Lactamase
• ISSN: 1751-7362; 1751-7370
• DOI: 10.1038/s41396-021-01130-6

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.