{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T20:45:34Z","timestamp":1782593134402,"version":"3.54.5"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":161,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cholera is a severe diarrheal disease caused by toxigenic Vibrio cholerae, whose virulence depends on lysogenic infection by CTX\u03c6 bacteriophages encoding the cholera toxin genes (ctxA and ctxB) and associated accessory genes (ace and zot). However, the global distribution and transmission dynamics of phage-encoded cholera toxin genes across environments remain poorly understood. To address this, we performed a large-scale bioinformatic analysis of publicly available whole genomes. We show that both phages and bacteria carrying toxin genes are globally distributed across human-associated, freshwater, fish, and mammalian habitats, with Vibrio and Aeromonas being the dominant bacterial taxa and Inoviridae is the most prevalent phage family. Phage-mediated horizontal gene transfer (HGT) of toxin genes occurred in both Vibrio and non-Vibrio species, with the highest transfer between Inoviridae and V. cholerae occuring predominantly among bacteria from the same habitat. Temporal analysis revealed an increase in candidate HGT events after 2000, peaking at 377845 events during 2010\u20132019. HGT events negatively correlated with the presence of CRISPR-Cas system and toxin-repression genes (hns, hapR, and tsrA) in host bacteria. Experimental validation indicated that H-NS and HapR inhibit phage infection by repressing phage release. Together, our results suggest that CRISPR-Cas phage defense system and toxin-repression mechanisms could constrain the spread of toxin-carrying phages, with potential implications for the occurrence and severity of cholera outbreaks worldwide.<\/jats:p>","DOI":"10.1093\/ismejo\/wrag139","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T11:35:33Z","timestamp":1781004933000},"source":"Crossref","is-referenced-by-count":0,"title":["Global transmission and distribution of phage-encoded cholera toxin genes constrained by toxin-repression genes and anti-phage defense systems"],"prefix":"10.1093","volume":"20","author":[{"given":"Shujian","family":"Yuan","sequence":"first","affiliation":[{"name":"Soil Ecology Lab, Jiangsu Provincial Key Laboratory of Coastal Saline Soil Resources Utilization and Ecological Conservation, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization & Jiangsu Key Laboratory for Solid Organic Waste Utilization, Nanjing Agricultural University , Nanjing 211800 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demeng","family":"Tan","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0826-6423","authenticated-orcid":false,"given":"Dong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Urban Environmental Processes and Pollution Control, Ningbo Urban Environment Observation and Research Station, Chinese Academy of Sciences , Ningbo 315800 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Balcazar","sequence":"additional","affiliation":[{"name":"Catalan Institute for Water Research (ICRA) , Girona 17003 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Nanjing Agricultural University , Nanjing 210095 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1592-157X","authenticated-orcid":false,"given":"Ville-Petri","family":"Friman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Helsinki , Helsinki 00014 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5550-6813","authenticated-orcid":false,"given":"Mingming","family":"Sun","sequence":"additional","affiliation":[{"name":"Soil Ecology Lab, Jiangsu Provincial Key Laboratory of Coastal Saline Soil Resources Utilization and Ecological Conservation, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization & Jiangsu Key Laboratory for Solid Organic Waste Utilization, Nanjing Agricultural University , Nanjing 211800 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Hu","sequence":"additional","affiliation":[{"name":"Soil Ecology Lab, Jiangsu Provincial Key Laboratory of Coastal Saline Soil Resources Utilization and Ecological Conservation, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization & Jiangsu Key Laboratory for Solid Organic Waste Utilization, Nanjing Agricultural University , Nanjing 211800 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"2026062716063153800_ref1","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1111\/1469-0691.12610","article-title":"Widespread epidemic cholera caused by a restricted subset of Vibrio cholerae 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