Global soil antibiotic resistance genes are associated with increasing risk and connectivity to human resistome

Yuxiang Zhao, Liguan Li, Yue Huang, Xiaoqing Xu, Zishu Liu, Shuxian Li, Lizhong Zhu, Baolan Hu () and Tong Zhang ()
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Yuxiang Zhao: The University of Hong Kong
Liguan Li: The University of Hong Kong
Yue Huang: The University of Hong Kong
Xiaoqing Xu: The University of Hong Kong
Zishu Liu: Zhejiang University
Shuxian Li: The University of Hong Kong
Lizhong Zhu: Zhejiang University
Baolan Hu: Zhejiang University
Tong Zhang: The University of Hong Kong

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Soil is a reservoir of antibiotic resistance genes (ARGs), and understanding its connection to human antibiotic resistome is crucial for the One Health framework. Rank I ARGs appear key to deciphering this relationship, but their global distribution and attribution in soil remain unclear. To fill this gap, we analyze 3965 metagenomic data (12 habitats, including soil, feces, sewage) and 8388 genomes of Escherichia coli isolates. Results show that soil ARG risk has increased over time (from 2008 to 2021). We introduce a “connectivity” metric that evaluates cross-habitat ARGs connectivity through sequence similarity and phylogenetic analysis, and reveal higher genetic overlap with clinical E. coli genomes (1985–2023) over time suggesting an increasing link between soil and human resistome. A comparison of 45 million genome pairs suggests that cross-habitat horizontal gene transfer (HGT) is crucial for the connectivity of ARGs between humans and soil. Finally, we compile clinical antibiotic resistance datasets (covering 126 countries from 1998 to 2022) and find significant correlations between soil ARG risk, potential HGT events and clinical antibiotic resistance (R2 = 0.40–0.89, p

Date: 2025
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DOI: 10.1038/s41467-025-61606-3

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