{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:35:53Z","timestamp":1791894953721,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2300302"],"award-info":[{"award-number":["2021YFC2300302"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>CTX\u03a6 is a lysogenic filamentous phage that carries the genes encoding cholera toxin (ctxAB), the main virulence factor of Vibrio cholerae. The toxigenic conversion of environmental V. cholerae strains through CTX\u03a6 lysogenic infection is crucial for the emergence of new pathogenic clones. A special allelic form of CTX\u03a6, called pre-CTX\u03a6, is a precursor of CTX\u03a6 and without ctxAB. Different members of the pre-CTX\u03a6 and CTX\u03a6 families are distinguished by the sequence of the transcriptional repressor-coding gene rstR. Multiple rstR alleles can coexist within a single strain, demonstrating the diverse structure and complex genomic integration patterns of CTX\u03a6\/pre-CTX\u03a6 prophage on the chromosome. Exploration of the diversity and co-integration patterns of CTX\u03a6\/pre-CTX\u03a6 prophages in V. cholerae can help to understand the evolution of this phage family. In this study, 21 V. cholerae strains, which were shown to carry the CTX\u03a6\/pre-CTX\u03a6 prophages as opposed to typical CTXET\u03a6-RS1 structure, were selected from approximately 1000 strains with diverse genomes. We identified two CTX\u03a6 members and six pre-CTX\u03a6 members with distinct rstR alleles, revealing complex chromosomal DNA integration patterns and arrangements of different prophages in these strains. Promoter activity assays showed that the transcriptional repressor RstR protected against CTX\u03a6 superinfection by preventing the replication and integration of CTX\u03a6\/pre-CTX\u03a6 phages containing the same rstR allele, supporting the co-integration of the diverse CTX\u03a6\/pre-CTX\u03a6 members observed. The numbers and types of prophages and their co-integration arrangements in serogroup O139 strains were more complex than those in serogroup O1 strains. Also, these CTX\u03a6\/pre-CTX\u03a6 members were shown to present the bloom period of the CTX\u03a6\/pre-CTX\u03a6 family during wave 2 of the seventh cholera pandemic. Together, these analyses deepen our comprehension of the genetic variation of CTX\u03a6 and pre-CTX\u03a6 and provide insights into the evolution of the CTX\u03a6\/pre-CTX\u03a6 family in the seventh cholera pandemic.<\/jats:p>","DOI":"10.3390\/microorganisms12101935","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T08:56:06Z","timestamp":1727168166000},"page":"1935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Diversity and Complexity of CTX\u03a6 and Pre-CTX\u03a6 Families in Vibrio cholerae from Seventh Pandemic"],"prefix":"10.3390","volume":"12","author":[{"given":"Xiaorui","family":"Li","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0759-0109","authenticated-orcid":false,"given":"Yu","family":"Han","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2069-4807","authenticated-orcid":false,"given":"Wenxuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9443-5803","authenticated-orcid":false,"given":"Yue","family":"Xiao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7090-8933","authenticated-orcid":false,"given":"Siyu","family":"Huang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenpeng","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenxia","family":"Fan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Liang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Kan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/S0140-6736(22)00330-0","article-title":"Cholera","volume":"399","author":"Kanungo","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ali, M., Nelson, A.R., Lopez, A.L., and Sack, D.A. 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