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High Throughput Co-culture Assays for the Investigation of Microbial Interactions
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Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community
Elizabeth M Adamowicz1, William R Harcombe2,3
1Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Antimicrobial Agents and Chemotherapy
|August 12, 2020
Summary
Predicting antibiotic interactions in polymicrobial infections is challenging. This study shows that monoculture antibiotic interaction patterns can predict coculture outcomes, aiding combination therapy development for resistant pathogens.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antimicrobial resistance (AMR) necessitates novel treatment strategies.
- Combination therapy is successful in cancer and HIV but challenging for bacterial infections.
- Polymicrobial infections complicate antibiotic treatment due to varied pathogen responses.
Purpose of the Study:
- To determine if monoculture antibiotic interaction patterns predict interactions in obligate cross-feeding cocultures.
- To test the weakest-link hypothesis for predicting antibiotic interactions in multispecies infections.
- To inform the design of effective combination therapies for complex bacterial infections.
Main Methods:
- Utilized checkerboard assays to test 10 antibiotic combinations.
- Observed antibiotic interactions (synergy, antagonism, additivity) in monocultures.
- Compared predicted coculture interactions (based on monoculture data and weakest-link hypothesis) with observed coculture interactions.
Main Results:
- Antibiotic combinations showed different interaction patterns in coculture compared to monoculture.
- Monoculture results, guided by the weakest-link hypothesis, were generally sufficient for predicting coculture interaction patterns.
- The study validated the weakest-link hypothesis in the context of cross-feeding cocultures.
Conclusions:
- Antibiotic interaction patterns observed in monocultures can predict outcomes in cross-feeding polymicrobial infections.
- The weakest-link hypothesis provides a framework for designing combination therapies for multispecies infections.
- This approach may facilitate the development of novel treatments to combat antimicrobial resistance.
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