1. Ecology
  2. Epidemiology and Global Health
Download icon

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
Research Article
  • Cited 0
  • Views 468
  • Annotations
Cite this article as: eLife 2021;10:e68764 doi: 10.7554/eLife.68764

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.

Reviewing Editor

  1. Gwenan M Knight, London School of Hygiene and Tropical Medicine, United Kingdom

Publication history

  1. Received: March 26, 2021
  2. Accepted: August 31, 2021
  3. Accepted Manuscript published: September 14, 2021 (version 1)

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

  • 468
    Page views
  • 88
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

  1. Further reading

Further reading

    1. Ecology
    2. Microbiology and Infectious Disease
    Matt Lloyd Jones et al.
    Research Article

    Common garden experiments that inoculate a standardised growth medium with synthetic microbial communities (i.e. constructed from individual isolates or using dilution cultures) suggest that the ability of the community to resist invasions by additional microbial taxa can be predicted by the overall community productivity (broadly defined as cumulative cell density and/or growth rate). However, to the best of our knowledge, no common garden study has yet investigated the relationship between microbial community composition and invasion resistance in microcosms whose compositional differences reflect natural, rather than laboratory-designed, variation. We conducted experimental invasions of two bacterial strains (Pseudomonas fluorescens and Pseudomonas putida) into laboratory microcosms inoculated with 680 different mixtures of bacteria derived from naturally occurring microbial communities collected in the field. Using 16S rRNA gene amplicon sequencing to characterise microcosm starting composition, and high-throughput assays of community phenotypes including productivity and invader survival, we determined that productivity is a key predictor of invasion resistance in natural microbial communities, substantially mediating the effect of composition on invasion resistance. The results suggest that similar general principles govern invasion in artificial and natural communities, and that factors affecting resident community productivity should be a focal point for future microbial invasion experiments.

    1. Biochemistry and Chemical Biology
    2. Ecology
    Milton T Drott
    Insight

    The fungus Aspergillus nidulans produces secondary metabolites during sexual development to protect itself from predators.