Global diversity and distribution of antibiotic resistance genes in human wastewater treatment systems

Congmin Zhu; Linwei Wu; Daliang Ning; Renmao Tian; Shuhong Gao; Bing Zhang; Jianshu Zhao; Ya Zhang; Naijia Xiao; Yajiao Wang; Mathew R Brown; Qichao Tu; Global Water Microbiome Consortium; Feng Ju; George F Wells; Jianhua Guo; Zhili He; Per H Nielsen; Aijie Wang; Yu Zhang; Ting Chen; Qiang He; Craig S Criddle; Michael Wagner; James M Tiedje; Thomas P Curtis; Xianghua Wen; Yunfeng Yang; Lisa Alvarez-Cohen; David A Stahl; Pedro J J Alvarez; Bruce E Rittmann; Jizhong Zhou

doi:10.1038/s41467-025-59019-3

Global diversity and distribution of antibiotic resistance genes in human wastewater treatment systems

Nat Commun. 2025 Apr 29;16(1):4006. doi: 10.1038/s41467-025-59019-3.

Authors

Congmin Zhu^#^{1

2

3}, Linwei Wu^#^{4

5}, Daliang Ning^#³, Renmao Tian^{3

6}, Shuhong Gao³, Bing Zhang^{7

8}, Jianshu Zhao⁹, Ya Zhang³, Naijia Xiao³, Yajiao Wang³, Mathew R Brown¹⁰, Qichao Tu¹¹; Global Water Microbiome Consortium; Feng Ju^{12

13}, George F Wells¹⁴, Jianhua Guo¹⁵, Zhili He^{16

17}, Per H Nielsen¹⁸, Aijie Wang¹⁹, Yu Zhang²⁰, Ting Chen²¹, Qiang He^{22

23}, Craig S Criddle²⁴, Michael Wagner²⁵, James M Tiedje²⁶, Thomas P Curtis¹⁰, Xianghua Wen⁷, Yunfeng Yang⁷, Lisa Alvarez-Cohen^{27

28}, David A Stahl²⁹, Pedro J J Alvarez³⁰, Bruce E Rittmann³¹, Jizhong Zhou^{32

33

34

35

36}

Collaborators

Global Water Microbiome Consortium:
Dany Acevedo, Miriam Agullo-Barcelo, Juliana Calabria de Araujo, Érika Ferreira de Abreu Mac Conell, Kevin Boehnke, Philip Bond, Charles B Bott, Patricia Bovio-Winkler, Rebecca K Brewster, Faizal Bux, Angela Cabezas, Léa Cabrol, Si Chen, Claudia Etchebehere, Amanda Ford, Janeth Sanabria Gómez, James S Griffin, April Z Gu, Moshe Habagil, Lauren Hale, Marc Harmon, Harald Horn, Zhiqiang Hu, David R Johnson, Deborah Garbani Marcantini, Alexander Keucken, Sheena Kumari, Cintia Dutra Leal, Zarraz Mp Lee, Yong Li, Zhenxin Li, Mengyan Li, Yu Liu, Leda C Mendonça-Hagler, Francisca Gleire Rodriguez de Menezes, Arthur J Meyers, Andrew Palmer, Prathap Parameswaran, Valeria Reginatto, Francis L de Los Reyes 3rd, Simona Rossetti, Jatinder Sidhu, Kylie Smith, Oscarina Viana de Sousa, Kyle Stephens, Chenxiang Sun, Nicholas B Tooker, Joy D Van Nostrand, Steve Wakelin, Bei Wang, Joseph E Weaver, Stephanie West, Sung-Geun Woo, Jer-Horng Wu, Liyou Wu, Chuanwu Xi, Tao Yan, Min Yang, Michelle Young, Chiqian Zhang, Qian Zhang, Wen Zhang, Wanlin Zheng, Hongde Zhou, Weiqin Zhuang

Affiliations

¹ School of Biomedical Engineering, Capital Medical University, Beijing, China.
² Beijing Key Laboratory of Fundamental Research on Biomechanics in Clinical Application, Capital Medical University, Beijing, China.
³ Institute for Environmental Genomics, University of Oklahoma, Norman, OK, USA.
⁴ Institute for Environmental Genomics, University of Oklahoma, Norman, OK, USA. linwei.wu@pku.edu.cn.
⁵ Institute of Ecology, Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China. linwei.wu@pku.edu.cn.
⁶ Institute for Food Safety and Health, Illinois Institute of Technology, Bedford Park, IL, USA.
⁷ State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing, China.
⁸ College of Life and Environmental Sciences, Minzu University of China, Beijing, China.
⁹ Center for Bioinformatics and Computational Biology, School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
¹⁰ School of Engineering, Newcastle University, Newcastle upon Tyne, UK.
¹¹ Institute for Marine Science and Technology, Shandong University, Qingdao, China.
¹² Key Laboratory of Coastal Environment and Resources of Zhejiang Province, School of Engineering, Westlake University, Hangzhou, Zhejiang, China.
¹³ Institute of Advanced Technology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
¹⁴ Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL, USA.
¹⁵ Australian Centre for Water and Environmental Biotechnology, The University of Queensland, Brisbane, Queensland, Australia.
¹⁶ Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, China.
¹⁷ College of Agronomy, Hunan Agricultural University, Changsha, China.
¹⁸ Department of Chemistry and Bioscience, Center for Microbial Communities, Aalborg University, Aalborg, Denmark.
¹⁹ Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
²⁰ State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
²¹ Institute for Artificial Intelligence and Department of Computer Science and Technology, Tsinghua University, Beijing, China.
²² Department of Civil and Environmental Engineering, The University of Tennessee, Knoxville, TN, USA.
²³ Institute for a Secure and Sustainable Environment, The University of Tennessee, Knoxville, TN, USA.
²⁴ Department of Civil and Environmental Engineering, Stanford University, Stanford, CA, USA.
²⁵ Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, Research Network 'Chemistry meets Microbiology', University of Vienna, Vienna, Austria.
²⁶ Center for Microbial Ecology, Michigan State University, East Lansing, MI, USA.
²⁷ Department of Civil and Environmental Engineering, College of Engineering, University of California, Berkeley, CA, USA.
²⁸ Earth and Environmental Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
²⁹ Department of Civil and Environmental Engineering, University of Washington, Seattle, WA, USA.
³⁰ Department of Civil and Environmental Engineering, Rice University, Houston, TX, USA.
³¹ Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, USA.
³² Institute for Environmental Genomics, University of Oklahoma, Norman, OK, USA. jzhou@ou.edu.
³³ Earth and Environmental Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. jzhou@ou.edu.
³⁴ School of Biological Sciences, University of Oklahoma, Norman, OK, USA. jzhou@ou.edu.
³⁵ School of Civil Engineering and Environmental Sciences, University of Oklahoma, Norman, OK, USA. jzhou@ou.edu.
³⁶ School of Computer Sciences, University of Oklahoma, Norman, OK, USA. jzhou@ou.edu.

^# Contributed equally.

Abstract

Antibiotic resistance poses a significant threat to human health, and wastewater treatment plants (WWTPs) are important reservoirs of antibiotic resistance genes (ARGs). Here, we analyze the antibiotic resistomes of 226 activated sludge samples from 142 WWTPs across six continents, using a consistent pipeline for sample collection, DNA sequencing and analysis. We find that ARGs are diverse and similarly abundant, with a core set of 20 ARGs present in all WWTPs. ARG composition differs across continents and is distinct from that of the human gut and the oceans. ARG composition strongly correlates with bacterial taxonomic composition, with Chloroflexi, Acidobacteria and Deltaproteobacteria being the major carriers. ARG abundance positively correlates with the presence of mobile genetic elements, and 57% of the 1112 recovered high-quality genomes possess putatively mobile ARGs. Resistome variations appear to be driven by a complex combination of stochastic processes and deterministic abiotic factors.

MeSH terms

Anti-Bacterial Agents / pharmacology
Bacteria* / classification
Bacteria* / drug effects
Bacteria* / genetics
Bacteria* / isolation & purification
Drug Resistance, Bacterial* / genetics
Drug Resistance, Microbial* / genetics
Genes, Bacterial*
Humans
Interspersed Repetitive Sequences / genetics
Sewage / microbiology
Wastewater* / microbiology
Water Purification

Substances

Wastewater
Sewage
Anti-Bacterial Agents

Abstract

MeSH terms

Substances

Grants and funding