Bacterial interspecies interactions modulate pH-mediated antibiotic tolerance
Abstract
Predicting antibiotic efficacy within microbial communities remains highly challenging. Interspecies interactions can impact antibiotic activity through many mechanisms, including alterations to bacterial physiology. Here, we studied synthetic communities constructed from the core members of the fruit fly gut microbiota. Co-culturing of Lactobacillus plantarum with Acetobacter species altered its tolerance to the transcriptional inhibitor rifampin. By measuring key metabolites and environmental pH, we determined that Acetobacter species counter the acidification driven by L. plantarum production of lactate. Shifts in pH were sufficient to modulate L. plantarum tolerance to rifampin and the translational inhibitor erythromycin. A reduction in lag time exiting stationary phase was linked to L. plantarum tolerance to rifampicin, opposite to a previously identified mode of tolerance to ampicillin in E. coli. This mechanistic understanding of the coupling among interspecies interactions, environmental pH, and antibiotic tolerance enables future predictions of growth and the effects of antibiotics in more complex communities.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files, excepting sequencing data that have been deposited in the sequence read archive of NCBI under accession number PRJNA530819 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA530819/).
Article and author information
Author details
Funding
National Institutes of Health (DP2OD006466)
- Kerwyn Casey Huang
National Science Foundation (MCB-1149328)
- Kerwyn Casey Huang
Allen Center for Systems Modeling of Infection (N/A)
- Kerwyn Casey Huang
National Institutes of Health (DP5OD017851)
- William B Ludington
Howard Hughes Medical Institute (International Student Research Fellowship)
- Andrés Aranda-Diaz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wenying Shou, Fred Hutchinson Cancer Research Center, United States
Publication history
- Received: August 30, 2019
- Accepted: January 28, 2020
- Accepted Manuscript published: January 29, 2020 (version 1)
- Version of Record published: February 17, 2020 (version 2)
Copyright
© 2020, Aranda-Diaz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Ecology
- Epidemiology and Global Health
The global spread of antibiotic resistance could be due to a number of factors, and not just the overuse of antibiotics in agriculture and medicine as previously thought.
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- Ecology
- Evolutionary Biology
How the ecological process of community assembly interacts with intra-species diversity and evolutionary change is a longstanding question. Two contrasting hypotheses have been proposed: Diversity Begets Diversity (DBD), in which taxa tend to become more diverse in already diverse communities, and Ecological Controls (EC), in which higher community diversity impedes diversification. Previously, using 16S rRNA gene amplicon data across a range of microbiomes, we showed a generally positive relationship between taxa diversity and community diversity at higher taxonomic levels, consistent with the predictions of DBD (Madi et al., 2020). However, this positive 'diversity slope' plateaus at high levels of community diversity. Here we show that this general pattern holds at much finer genetic resolution, by analyzing intra-species strain and nucleotide variation in static and temporally sampled metagenomes from the human gut microbiome. Consistent with DBD, both intra-species polymorphism and strain number were positively correlated with community Shannon diversity. Shannon diversity is also predictive of increases in polymorphism over time scales up to ~4-6 months, after which the diversity slope flattens and becomes negative – consistent with DBD eventually giving way to EC. Finally, we show that higher community diversity predicts gene loss at a future time point. This observation is broadly consistent with the Black Queen Hypothesis, which posits that genes with functions provided by the community are less likely to be retained in a focal species' genome. Together, our results show that a mixture of DBD, EC, and Black Queen may operate simultaneously in the human gut microbiome, adding to a growing body of evidence that these eco-evolutionary processes are key drivers of biodiversity and ecosystem function.