Delayed antibiotic exposure induces population collapse in enterococcal communities with drug-resistant subpopulations

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Abstract

The molecular underpinnings of antibiotic resistance are increasingly understood, but less is known about how these molecular events influence microbial dynamics on the population scale. Here we show that the dynamics of E. faecalis communities exposed to antibiotics can be surprisingly rich, revealing scenarios where increasing population size or delaying drug exposure can promote population collapse. Specifically, we demonstrate how density-dependent feedback loops couple population growth and antibiotic efficacy when communities include drug-resistant subpopulations, leading to a wide range of behavior, including population survival, collapse, or one of two qualitatively distinct bistable behaviors where survival is favored in either small or large populations. These dynamics reflect competing density-dependent effects of different subpopulations, with growth of drug-sensitive cells increasing but growth of drug-resistant cells decreasing effective drug inhibition. Finally, we demonstrate how populations receiving immediate drug influx may sometimes thrive, while identical populations exposed to delayed drug influx collapse.

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All experimental data are included in the manuscript and supporting files.

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Kelsey M Hallinen

Department of Biophysics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4081-6699
Jason Karslake

Department of Biophysics, University of Michigan, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Kevin B Wood

Department of Biophysics, University of Michigan, Ann Arbor, United States

For correspondence
kbwood@umich.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0985-7401

Funding

National Science Foundation (1553028)

Kevin B Wood

National Institute of General Medical Sciences (1R35GM124875)

Kevin B Wood

National Science Foundation (GRFP)

Kelsey M Hallinen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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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.