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Plasmids, a molecular cornerstone of antimicrobial resistance in the One Health era

Nature Reviews Microbiology volume 22, pages 18–32 (2024)Cite this article

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Abstract

Antimicrobial resistance (AMR) poses a substantial threat to human health. The widespread prevalence of AMR is, in part, due to the horizontal transfer of antibiotic resistance genes (ARGs), typically mediated by plasmids. Many of the plasmid-mediated resistance genes in pathogens originate from environmental, animal or human habitats. Despite evidence that plasmids mobilize ARGs between these habitats, we have a limited understanding of the ecological and evolutionary trajectories that facilitate the emergence of multidrug resistance (MDR) plasmids in clinical pathogens. One Health, a holistic framework, enables exploration of these knowledge gaps. In this Review, we provide an overview of how plasmids drive local and global AMR spread and link different habitats. We explore some of the emerging studies integrating an eco-evolutionary perspective, opening up a discussion about the factors that affect the ecology and evolution of plasmids in complex microbial communities. Specifically, we discuss how the emergence and persistence of MDR plasmids can be affected by varying selective conditions, spatial structure, environmental heterogeneity, temporal variation and coexistence with other members of the microbiome. These factors, along with others yet to be investigated, collectively determine the emergence and transfer of plasmid-mediated AMR within and between habitats at the local and global scale.

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Fig. 1: Mechanisms of horizontal gene transfer.
Fig. 2: Antibiotic resistance gene spread in a One Health framework.
Fig. 3: The role of plasmids in the dissemination of antimicrobial resistance genes across habitats.
Fig. 4: Factors driving plasmid fate.

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Acknowledgements

The authors thank C. Elg and O. Kosterlitz for critical reading of this manuscript and B. Robison for helpful discussions on data visualization. The authors were partially supported by the National Institute of Food and Agriculture (NIFA) (grant 2018–67017–27630) of the US Department of Agriculture; the National Institute of Allergy and Infectious Diseases Extramural Activities (grant R01 AI084918) of the National Institutes of Health (NIH); and the Bioinformatics and Computational Biology Program at the University of Idaho in partnership with the Institute for Bioinformatics and Evolutionary Studies (now the Institute for Interdisciplinary Data Sciences (IIDS)).

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  1. Department of Biological Sciences, University of Idaho, Moscow, ID, USA

    Salvador Castañeda-Barba, Eva M. Top & Thibault Stalder

  2. Bioinformatics and Computational Biology Graduate Program, University of Idaho, Moscow, ID, USA

    Salvador Castañeda-Barba & Eva M. Top

  3. Institute for Interdisciplinary Data Sciences, University of Idaho, Moscow, ID, USA

    Salvador Castañeda-Barba, Eva M. Top & Thibault Stalder

  4. Institute for Modelling Collaboration and Innovation, University of Idaho, Moscow, ID, USA

    Eva M. Top & Thibault Stalder

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S.C.-B. and T.S. contributed to the discussion of content and literature collection and wrote the article. S.C.-B. performed the meta-analysis. E.M.T. provided critical reviews throughout the process. All authors thoroughly reviewed and edited the article.

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Glossary

Eco-evolutionary

(Perspectives, approaches, studies, factors, trajectories). Refers to the fact that interactions between ecological and evolutionary processes are reciprocal.

Habitat

A place where bacteria live, from the human body to any natural environment, including all biotic and abiotic factors of their surroundings.

One Health

Definition from the One Health High-Level Expert Panel (OHHLEP): an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals and ecosystems. One Health recognizes that the health of humans, domestic and wild animals, plants and the wider environment (including ecosystems) is closely linked and interdependent. The approach mobilizes multiple sectors, disciplines and communities at varying levels of society to work together to foster well-being and tackle threats to health and ecosystems, while addressing the collective need for healthy food, water, energy and air, taking action on climate change and contributing to sustainable development.

Plasmid persistence

The ability of a plasmid to maintain itself in a population or community in the presence or absence of known selection for the plasmid.

Plasmid stability

The ability of a plasmid to maintain itself in a population in the absence of known selection for the plasmid.

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Castañeda-Barba, S., Top, E.M. & Stalder, T. Plasmids, a molecular cornerstone of antimicrobial resistance in the One Health era. Nat Rev Microbiol 22, 18–32 (2024). https://doi.org/10.1038/s41579-023-00926-x

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