An omics-based framework for assessing the health risk of antimicrobial resistance genes

An-Ni Zhang, Jeffry M. Gaston, Chengzhen L. Dai, Shijie Zhao, Mathilde Poyet, Mathieu Groussin, Xiaole Yin, Li-Guan Li, Mark C. M. van Loosdrecht, Edward Topp, Michael R. Gillings, William P. Hanage, James M. Tiedje, Katya Moniz, Eric J. Alm, Tong Zhang*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    203 Citations (Scopus)
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    Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an ‘omics-based’ framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as ‘current threats’ (Rank I; 3%) - already present among pathogens - and ‘future threats’ (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 ‘current threat’ ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II (‘future threats’). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.

    Original languageEnglish
    Article number4765
    Pages (from-to)1-11
    Number of pages11
    JournalNature Communications
    Issue number1
    Publication statusPublished - 6 Aug 2021

    Bibliographical note

    Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


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