安普霉素耐药大肠埃希菌在人群与动物生产环节的分布与传播——一项多中心、横断面及“全健康”研究

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

工程（英文） ›› 2026, Vol. 60 ›› Issue (5) : 116 -126. DOI: 10.1016/j.eng.2025.11.035

研究论文

安普霉素耐药大肠埃希菌在人群与动物生产环节的分布与传播——一项多中心、横断面及“全健康”研究

ⁱ

Yue Cao ^a^,¹ ,
Dejun Liu ^a^,¹ ,
Fen Pan ^b^,¹ ,
Zhenzhen Liu ^c^,¹ ,
Qin Zhang ^d^,¹ ,
Chengtao Sun ^a^,¹ ,
Li Ding ^e ,
Siquan Shen ^e ,
Weishuai Zhai ^f ,
Rina Bai ^a ,
Zhiyu Zou ^a ,
Yiqing Wang ^a ,
Lu Yang ^g ,
Zexun Lv ^a ,
Bo Fu ^a ,
Shizhen Ma ^a ,
Yao Wang ^f ,
Ke Zhao ^a ,
Tingxuan Shi ^a ,
Yingbo Shen ^a ,
Rong Zhang ^h ,
Timothy R. Walsh ⁱ^,^* ,
Jianzhong Shen ^a^,^* ,
Fupin Hu ^e^,^* ,
Yang Wang ^a^,^* ,
Congming Wu ^a^,^*

作者信息 +

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

Yue Cao ^a^,¹ ,
Dejun Liu ^a^,¹ ,
Fen Pan ^b^,¹ ,
Zhenzhen Liu ^c^,¹ ,
Qin Zhang ^d^,¹ ,
Chengtao Sun ^a^,¹ ,
Li Ding ^e ,
Siquan Shen ^e ,
Weishuai Zhai ^f ,
Rina Bai ^a ,
Zhiyu Zou ^a ,
Yiqing Wang ^a ,
Lu Yang ^g ,
Zexun Lv ^a ,
Bo Fu ^a ,
Shizhen Ma ^a ,
Yao Wang ^f ,
Ke Zhao ^a ,
Tingxuan Shi ^a ,
Yingbo Shen ^a ,
Rong Zhang ^h ,
Timothy R. Walsh ⁱ^,^* ,
Jianzhong Shen ^a^,^* ,
Fupin Hu ^e^,^* ,
Yang Wang ^a^,^* ,
Congming Wu ^a^,^*

Author information +

^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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文章历史 +

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摘要

安普霉素是一种兽医专用氨基糖苷类抗生素，因其毒性较低且对多重耐药菌具有较强的抗菌活性，其临床应用潜力日益受到关注。尽管已完成两项Ⅰ期临床试验，但安普霉素耐药性在“全健康”不同界面间的传播动态仍不清楚。本研究于2020年至2023年期间，在中国成都、青岛和上海三地展开，共采集了5160份独立样本，来源涵盖医院、肉鸡与生猪养殖场、屠宰场以及销售市场等多种场所。共鉴定出1394株安普霉素耐药大肠埃希菌（apramycin-resistant Escherichia coli, AREC），其中在动物粪便中的检出率最高（58%，700/1214），其次依次为动物胴体（47%，183/393）、市售鲜肉（35%，229/659）、环境样本（21%，127/593）、人群粪便（7%，103/1425）及临床感染样本（5%，42/876）。从生产链角度来看，肉鸡生产链的检出率（57%，742/1292）高于生猪生产链（32%，512/1609）。绝大多数耐药分离株（99.7%，1390/1394）携带aac(3)-IV基因，该基因介导对安普霉素、庆大霉素和妥布霉素的耐药。对742株分离株的基因组分析表明，青岛和上海两地存在动物与人之间的散发性克隆传播事件。对66株代表菌株的长读长测序显示，aac(3)-IV基因主要位于IncHI2/IncHI2A质粒上，且在不同来源质粒中结构高度保守。历时监测数据显示，自安普霉素在我国畜牧业投入应用以来，畜禽来源大肠埃希菌中aac(3)-IV基因的流行率迅速上升。本研究揭示了安普霉素耐药性在“全健康”体系内经质粒快速传播的现象，提示有必要加强兽用抗生素的审慎管理，并对将安普霉素转用于人类临床治疗的可能性进行慎重评估。

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.

关键词

安普霉素耐药性 / 大肠埃希菌 / 全健康 / IncHI2/IncHI2A 质粒 / aac(3)-IV

Key words

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. 安普霉素耐药大肠埃希菌在人群与动物生产环节的分布与传播——一项多中心、横断面及“全健康”研究[J]. 工程（英文）, 2026, 60(5): 116-126 DOI:10.1016/j.eng.2025.11.035