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These bacteria acquire resistance by incorporating various antibiotic resistance genes (ARGs) through specialized gene transfer mechanisms, allowing them to evade antibiotic attacks. Conjugation, transformation, and transduction are well\u2010established mechanisms that drive the acquisition and dissemination of ARGs in Gram\u2010negative bacteria. In particular, the horizontal transfer of plasmids carrying multiple ARGs is highly problematic, as it can instantly convert susceptible bacteria into multidrug\u2010resistant ones. Transduction, mediated by bacteriophages that package ARG\u2010containing chromosomal DNA from host cells, also plays a crucial role in ARG spread without requiring direct cell\u2010to\u2010cell contact. Recently, a novel horizontal gene transfer (HGT) mechanism involving outer membrane vesicles (OMVs) has been identified as a key player in ARG dissemination. OMVs\u2014nanoscale, spherical structures produced by bacteria during growth\u2014have been found to carry small plasmids and chromosomal DNA fragments containing ARGs from their host bacteria. This newly discovered transfer process, termed \u201cvesiduction,\u201d enables intercellular DNA exchange and further contributes to the spread of antibiotic resistance. Additionally, mobile genetic elements such as transposons, insertion sequences, and site\u2010specific recombination systems like integrons facilitate rearrangement of ARGs, including their translocation between chromosomes and plasmids. This review explores the molecular mechanisms underlying the HGT of ARGs, with a particular focus on clinically isolated antibiotic\u2010resistant Gram\u2010negative bacteria.<\/jats:p>","DOI":"10.1111\/1348-0421.13222","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T04:19:10Z","timestamp":1747282750000},"page":"367-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Horizontal Gene Transfer Systems for Spread of Antibiotic Resistance in Gram\u2010Negative Bacteria"],"prefix":"10.1111","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2619-8380","authenticated-orcid":false,"given":"Jun\u2010ichi","family":"Wachino","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology Faculty of Medical Sciences, Fujita Health University Toyoake Aichi 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