Bacterial interspecies interactions modulate pH-mediated antibiotic tolerance

Andrés Aranda-Díaz,Zachary F Hallberg,Ren Dodge,Benjamin Obadia,Zehra Tüzün Güvener,Kerwyn Casey Huang,Tani Thomsen,William B Ludington

doi:10.7554/elife.51493

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.

Highlights

Decades of investigations have described detailed and precise molecular mechanisms of antibiotic action using model organisms such as Escherichia coli grown in monoculture
We identified five species belonging to seven unique operational taxonomic units (OTUs) by clustering the sequences at 99% identity: L. plantarum (Lp), L. brevis (Lb), Acetobacter pasteurianus (Ap), A. tropicalis (At), and A. aceti (Aa) (Figure 1A)
The pH-based mechanism underlying the tolerance of Lactobacillus plantarum (Lp) induced by Acetobacter species is intrinsically connected to the metabolic capacity of each species, and is likely to be generally relevant in more complex communities

Summary

Introduction

Decades of investigations have described detailed and precise molecular mechanisms of antibiotic action using model organisms such as Escherichia coli grown in monoculture. Ecology Microbiology and Infectious Disease environmental variables modified by bacterial activity An example of the latter is pH, which has recently been shown to drive community dynamics in an artificial laboratory system of decomposition bacteria (Ratzke and Gore, 2018). The gut microbiota of Drosophila melanogaster fruit flies is such a low diversity assemblage in which all members can be cultured in vitro (Obadia et al, 2017), making it amenable to the systematic dissection of bacterial interactions. This community consists of ~5 species predominantly from the Lactobacillus and Acetobacter genera (Wong et al, 2011) (Figure 1A). Changes in the survivability of Lactobacillus plantarum (Lp) when co-cultured with Acetobacter pasteurianus (Ap) are not due to increased survivability of Ap, inoculum size, or Lp growth in rifampin

Results

Discussion

Materials and methods

Funding Funder National Institutes of Health