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While strains responsible for cholera have been extensively studied over the past century, less is known about their environmental counterparts, despite their contributions to the species\u2019 pangenome. This study analyzed the genome compositions of 46 V. cholerae strains, including pandemic and nonpandemic, toxigenic, and environmental variants, to investigate the diversity of mobile genetic elements (MGEs), embedded bacterial defense systems, and phage-associated signatures. Our findings include both conserved and novel MGEs across strains, pointing to shared evolutionary pathways and ecological niches. The defensome analysis revealed a wide array of antiphage\/antiplasmid mechanisms, extending well beyond the traditional CRISPR-Cas and restriction-modification systems. This underscores the dynamic arms race between V. cholerae and MGEs and suggests that nonpandemic strains may act as reservoirs for emerging defense strategies. Moreover, the study showed that MGEs are integrated into genomic hotspots, which may serve as critical platforms for the exchange of defense systems, thereby enhancing V. cholerae's adaptive capabilities against phage attacks and other invading MGEs. Overall, this research offers new insights into V. cholerae's genetic complexity and potential adaptive strategies, offering a better understanding of the differences between environmental strains and their pandemic counterparts, as well as the possible evolutionary pathways that led to the emergence of pandemic strains.<\/jats:p>","DOI":"10.1093\/gbe\/evaf079","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T01:36:43Z","timestamp":1745977003000},"source":"Crossref","is-referenced-by-count":10,"title":["Exploring Mobile Genetic Elements in\n                    <i>Vibrio cholerae<\/i>"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4088-8548","authenticated-orcid":false,"given":"Nat\u00e1lia C","family":"Drebes D\u00f6rr","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) , CH-1015 Lausanne ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7997-5526","authenticated-orcid":false,"given":"Alexandre","family":"Lemopoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) , CH-1015 Lausanne ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7024-1489","authenticated-orcid":false,"given":"Melanie","family":"Blokesch","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) , CH-1015 Lausanne 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