Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: a modelling study applied to nosocomial pathogen control

  1. David R M Smith  Is a corresponding author
  2. Laura Temime
  3. Lulla Opatowski
  1. Institut Pasteur, France
  2. Conservatoire national des arts et métiers, France

Abstract

The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modelling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens (Clostridioides difficile, methicillin-resistant Staphylococcus aureus, multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.

Data availability

Model equations and parameter values are provided in the manuscript, as well as in supporting R files and a Mathematica notebook available online at https://github.com/drmsmith/microbiomeR

Article and author information

Author details

  1. David R M Smith

    Global Health, Institut Pasteur, Paris, France
    For correspondence
    david.smith@pasteur.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7330-4262
  2. Laura Temime

    MESuRS, Conservatoire national des arts et métiers, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8850-5403
  3. Lulla Opatowski

    Global Health, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

Funding

Agence Nationale de la Recherche (SPHINX-17-CE36-0008-01)

  • David R M Smith

Canadian Institutes of Health Research (Doctoral Foreign Study Award 164263)

  • David R M Smith

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

Copyright

© 2021, Smith 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.

Metrics

  • 2,294
    views
  • 381
    downloads
  • 11
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. David R M Smith
  2. Laura Temime
  3. Lulla Opatowski
(2021)
Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: a modelling study applied to nosocomial pathogen control
eLife 10:e68764.
https://doi.org/10.7554/eLife.68764

Share this article

https://doi.org/10.7554/eLife.68764

Further reading

    1. Ecology
    Itai Bloch, David Troupin ... Nir Sapir
    Research Article

    Optimal foraging theory posits that foragers adjust their movements based on prey abundance to optimize food intake. While extensively studied in terrestrial and marine environments, aerial foraging has remained relatively unexplored due to technological limitations. This study, uniquely combining BirdScan-MR1 radar and the Advanced Tracking and Localization of Animals in Real-Life Systems biotelemetry system, investigates the foraging dynamics of Little Swifts (Apus affinis) in response to insect movements over Israel’s Hula Valley. Insect movement traffic rate (MoTR) substantially varied across days, strongly influencing swift movement. On days with high MoTR, swifts exhibited reduced flight distance, increased colony visit rate, and earlier arrivals at the breeding colony, reflecting a dynamic response to prey availability. However, no significant effects were observed in total foraging duration, flight speed, or daily route length. Notably, as insect abundance increased, inter-individual distances decreased. These findings suggest that Little Swifts optimize their foraging behavior in relation to aerial insect abundance, likely influencing reproductive success and population dynamics. The integration of radar technology and biotelemetry systems provides a unique perspective on the interactions between aerial insectivores and their prey, contributing to a comprehensive understanding of optimal foraging strategies in diverse environments.

    1. Ecology
    2. Evolutionary Biology
    Rebecca D Tarvin, Jeffrey L Coleman ... Richard W Fitch
    Research Article

    Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs of the family Dendrobatidae have evolved the novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling for alkaloids has been biased towards colorful species, without similar attention paid to inconspicuous ones that are often assumed to be undefended. As a result, our understanding of how chemical defense evolved in this group is incomplete. Here, we provide new data showing that, in contrast to previous studies, species from each undefended poison frog clade have measurable yet low amounts of alkaloids. We confirm that undefended dendrobatids regularly consume mites and ants, which are known sources of alkaloids. Thus, our data suggest that diet is insufficient to explain the defended phenotype. Our data support the existence of a phenotypic intermediate between toxin consumption and sequestration — passive accumulation — that differs from sequestration in that it involves no derived forms of transport and storage mechanisms yet results in low levels of toxin accumulation. We discuss the concept of passive accumulation and its potential role in the origin of chemical defenses in poison frogs and other toxin-sequestering organisms. In light of ideas from pharmacokinetics, we incorporate new and old data from poison frogs into an evolutionary model that could help explain the origins of acquired chemical defenses in animals and provide insight into the molecular processes that govern the fate of ingested toxins.