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Inter-species interactions alter antibiotic efficacy in bacterial communities
Michael J Bottery1,2, Jessica L Matthews3, A Jamie Wood3,4
1Division of Evolution, Infection and Genomics, University of Manchester, Manchester, M13 9PL, UK. michael.bottery@manchester.ac.uk.
The ISME Journal
|October 10, 2021
Summary
Interactions within microbial communities significantly alter antibiotic effectiveness. Stenotrophomonas maltophilia protects Pseudomonas aeruginosa from imipenem by neutralizing the drug, demonstrating the impact of microbial ecology on antibiotic treatment success.
Area of Science:
- Microbiology
- Medical Microbiology
- Antimicrobial Resistance
Background:
- Conventional in vitro antibiotic susceptibility testing (e.g., minimum inhibitory concentration or MIC) often fails to predict treatment efficacy in polymicrobial infections.
- Inter-species interactions within microbial communities can modulate the susceptibility of individual species to antibiotics.
Purpose of the Study:
- To quantify and elucidate the mechanisms behind community-modulated antibiotic efficacy against Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities.
- To investigate the protective effects of Stenotrophomonas maltophilia on P. aeruginosa in polymicrobial settings.
Main Methods:
- Utilized model CF lung communities derived from clinical samples.
- Assessed antibiotic efficacy using clinically relevant antibiotics, including carbapenems like imipenem and meropenem.
- Employed mathematical ordinary differential equation modeling to analyze antibiotic inactivation and efficacy.
Main Results:
- Multi-drug resistant S. maltophilia provided significant protection to sensitive P. aeruginosa against imipenem, increasing its MIC up to 16-fold.
- Protection was mediated by chromosomally encoded metallo-β-lactamase activity of S. maltophilia, which detoxified the antibiotic in an environment- and cell-density-dependent manner.
- S. maltophilia did not confer protection against meropenem, highlighting differential effects of antibiotics.
- Mathematical modeling explained the varying protection levels based on antibiotic efficacy and inactivation rates.
Conclusions:
- Inter-species interactions and pre-existing antimicrobial resistance mechanisms within polymicrobial communities profoundly impact pathogen antibiotic susceptibility.
- Microbial ecology plays a critical role in determining the success of antibiotic treatments for complex infections.
- Current in vitro susceptibility testing methods may require refinement to account for community dynamics in clinical settings.
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