Distribution and Transmission of Apramycin-Resistant Escherichia coli from Humans and Animal-Producing Sectors: A Multicenter, Cross-sectional, and One Health Study

Yue Cao; Dejun Liu; Fen Pan; Zhenzhen Liu; Qin Zhang; Chengtao Sun; Li Ding; Siquan Shen; Weishuai Zhai; Rina Bai; Zhiyu Zou; Yiqing Wang; Lu Yang; Zexun Lv; Bo Fu; Shizhen Ma; Yao Wang; Ke Zhao; Tingxuan Shi; Yingbo Shen; Rong Zhang; Timothy R. Walsh; Jianzhong Shen; Fupin Hu; Yang Wang; Congming Wu

doi:10.1016/j.eng.2025.11.035

Engineering ›› :202511035 DOI: 10.1016/j.eng.2025.11.035

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Distribution and Transmission of Apramycin-Resistant Escherichia coli from Humans and Animal-Producing Sectors: A Multicenter, Cross-sectional, and One Health Study

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^a National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China

^b Department of Clinical Laboratory, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China

^c Department of Laboratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266000, China

^d Chengdu Women’s and Children’s Central Hospital, Chengdu 610017, China

^e Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China

^f Technology Innovation Centre for Food Safety Surveillance and Detection (Hainan), Sanya Institute of China Agricultural University, Sanya 572025, China

^g Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

^h Department of Clinical Laboratory, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China

ⁱ Ineos Oxford Institute for Antimicrobial Research, Department of Biology, University of Oxford, Oxford OX1 3SZ, UK

^* timothy.walsh@biology.ox.ac.uk (Timothy R. Walsh),

sjz@cau.edu.cn (Jianzhong Shen),

hufupin@fudan.edu.cn (Fupin Hu),

wangyang@cau.edu.cn (Yang Wang),

wucm@cau.edu.cn (Congming Wu)

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Abstract

Apramycin, an aminoglycoside antibiotic used exclusively in veterinary medicine, has attracted growing interest for its potential clinical application owing to its low toxicity and potent activity against multidrug-resistant (MDR) bacteria. Despite the completion of two Phase I clinical trials, apramycin resistance dynamics across One Health interfaces remain poorly understood. This study, conducted from 2020 to 2023 in Chengdu, Qingdao, and Shanghai, China, collected 5160 non-duplicate samples from hospitals, broiler and pig farms and slaughterhouses, and markets. We identified 1394 isolates of apramycin-resistant Escherichia coli (E. coli ) (AREC), with the highest detection rates in animal feces (58%, 700/1214), followed by animal carcasses (47%, 183/393), fresh meat (35%, 229/659), environments (21%, 127/593), human feces (7%, 103/1425), and clinical samples (5%, 42/876). Detection rates were higher in broiler-producing chains (57%, 742/1292) than in pig-producing chains (32%, 512/1609). Most AREC isolates (99.7%, 1390/1394) carried the aac(3)-IV gene, conferring resistance to apramycin, gentamicin, and tobramycin. Genomic analysis of 742 AREC isolates revealed sporadic clonal transmission events between animals and humans in Qingdao and Shanghai. Long-read sequencing of 66 representative isolates showed that aac(3)-IV genes were primarily located on IncHI2/IncHI2A plasmids, with high structural conservation across different sources. Temporal surveillance indicated a sharp increase in aac(3)-IV prevalence in livestock-associated E. coli following the adoption of apramycin in China. These findings demonstrate the rapid, plasmid-driven dissemination of apramycin resistance at the One Health interface, underscore the need for prudent veterinary stewardship and careful consideration of apramycin’s clinical repurposing for human use.

Keywords

Apramycin resistance / Escherichia coli / One Health / IncHI2/IncHI2A plasmids / aac(3)-IV

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Yue Cao, Dejun Liu, Fen Pan, Zhenzhen Liu, Qin Zhang, Chengtao Sun, Li Ding, Siquan Shen, Weishuai Zhai, Rina Bai, Zhiyu Zou, Yiqing Wang, Lu Yang, Zexun Lv, Bo Fu, Shizhen Ma, Yao Wang, Ke Zhao, Tingxuan Shi, Yingbo Shen, Rong Zhang, Timothy R. Walsh, Jianzhong Shen, Fupin Hu, Yang Wang, Congming Wu. Distribution and Transmission of Apramycin-Resistant Escherichia coli from Humans and Animal-Producing Sectors: A Multicenter, Cross-sectional, and One Health Study. Engineering 202511035 DOI:10.1016/j.eng.2025.11.035

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