{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:20:55Z","timestamp":1785338455597,"version":"3.55.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":329,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Macrolide antibiotics are vital for controlling infections in humans, animals, and agriculture, yet their effectiveness is increasingly compromised by antimicrobial resistance. Macrolide esterases (MLEs) are key mediators of macrolide resistance but have only been detected in Gram-negative bacteria, with no evidence in Gram-positive species. Here, we mined over 500\u2009000 Gram-positive genomes and identified 8707 candidate proteins. Six representative MLEs were functionally validated, conferring resistance to 16-membered macrolides and increasing minimum inhibitory concentrations (MICs) up to 16-fold in Escherichia coli and 128-fold in Bacillus subtilis. Moreover, two exhibited broad-spectrum activity against all clinically and veterinary relevant 16-membered macrolides. Temporal analysis revealed that Gram-positive MLEs originated at least 2.7 million years ago, contrasting with their emergence in Gram-negative bacteria after the introduction of antibiotics. Genomic surveys further demonstrated the global distribution of MLE-carrying Gram-positive bacteria across 97 countries and diverse ecosystems, including clinical, food, agricultural, and natural environments. These findings highlight Gram-positive MLEs as an underrecognized risk and underscore the need for a One Health\u2013oriented strategy to monitor, assess, and mitigate the spread of macrolide resistance across interconnected ecosystems.<\/jats:p>","DOI":"10.1093\/ismejo\/wraf261","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T12:57:11Z","timestamp":1764075431000},"source":"Crossref","is-referenced-by-count":3,"title":["Global distribution of \u03b1\/\u03b2 hydrolase family macrolide esterases in Gram-positive bacteria"],"prefix":"10.1093","volume":"19","author":[{"given":"Yang","family":"Zhou","sequence":"first","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, Center for Pathogen Research, West China Hospital, Sichuan University , Chengdu , Sichuan 610106,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Mao","sequence":"additional","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangqun","family":"Hou","sequence":"additional","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Chu","sequence":"additional","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Wang","sequence":"additional","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Geohazard Prevention and Geoenvironment Protection, College of Ecology and Environment, Chengdu University of Technology , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University , Qingdao, Shandong 266237 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University , Chengdu, Sichuan 610106 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likai","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, CAS , Guiyang, Guizhou 550081 ,","place":["PR China"]},{"name":"College of Resources and Environment, University of Chinese Academy of Sciences , Beijing 100049 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University , Qingdao, Shandong 266237 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafu","family":"Lin","sequence":"additional","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3728-7973","authenticated-orcid":false,"given":"Tao","family":"Song","sequence":"additional","affiliation":[{"name":"Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of pharmacy, Chengdu University , Chengdu, Sichuan 610106 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