Bacterial interspecies interactions modulate pH-mediated antibiotic tolerance

Abstract
Data availability
Article and author information
Metrics

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/).

The following data sets were generated

1. Ludington W
(2019) Laboratory Drosophila melanogaster gut microbiome
NCBI SRA, PRJNA530819.

https://www.ncbi.nlm.nih.gov/bioproject/PRJNA530819/

Article and author information

Author details

Andrés Aranda-Diaz

Department of Bioengineering, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0566-4901
Benjamin Obadia

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3286-3236
Ren Dodge

Department of Embryology, Carnegie Institute, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Tani Thomsen

Department of Bioengineering, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Zachary F Hallberg

Department of Chemistry, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Zehra Tüzün Güvener

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
William B Ludington

Department of Embryology, Carnegie Institute, Baltimore, United States

For correspondence
ludington@carnegiescience.edu

Competing interests
The authors declare that no competing interests exist.
Kerwyn Casey Huang

Department of Bioengineering, Stanford University, Stanford, United States

For correspondence
kchuang@stanford.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8043-8138

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.

Copyright

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.