{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:10:20Z","timestamp":1791947420921,"version":"4.3.4"},"reference-count":160,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"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":["2024YFC3406300"],"award-info":[{"award-number":["2024YFC3406300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Laboratory of Veterinary Public Health and Safety Open Project Fund","award":["2024SKLVPHS04"],"award-info":[{"award-number":["2024SKLVPHS04"]}]},{"name":"Fundamental Research Funds of Taizhou University","award":["TZXYQD2024A034"],"award-info":[{"award-number":["TZXYQD2024A034"]}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to treat MDR bacteria, is of particular concern. Colistin has been recognized as a last-line antibiotic for the treatment of MDR Gram-negative bacterial infections caused by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Recently, the increasing reports of colistin resistance pose a significant threat to public health, caused by both acquired and intrinsic mechanisms. The review aimed to elucidate the trends in colistin resistance, the use of colistin in human and veterinary medicine, underlying resistance mechanisms and transmission pathways, and potential mitigation of this emerging threat through novel intervention strategies. Colistin resistance is mediated by plasmid-encoded phosphoethanolamine transferases (mcr-1 to mcr-10) and chromosomal lipid A remodeling pathways. In Escherichia coli, resistance involves mcr-1\u201310, acrB efflux mutations, pmrA\/pmrB, arnBCADTEF, and mgrB inactivation. Klebsiella pneumoniae exhibits mcr-1, mcr-8, mcr-9, mgrB disruption and phoP\/phoQ\u2013pmrAB activation. Acinetobacter baumannii harbors mcr-1\u20134, while Salmonella enterica and Enterobacter spp. carry mcr variants with arnBCADTEF induction. Therapeutic options include adjunct strategies such as antimicrobial peptides, nanomaterials, therapeutic adjuvants, CRISPR-Cas9-based gene editing, probiotics, vaccines, and immune modulators to restore susceptibility. This review identified that specific and wide actions are required to handle the growing colistin resistance, including genomic surveillance, tracing novel resistance mechanisms, and the application of alternative management strategies. The One Health approach is considered a key strategy to address this growing issue.<\/jats:p>","DOI":"10.3390\/microorganisms14010173","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T11:42:58Z","timestamp":1768304578000},"page":"173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Colistin Resistance in Gram-Negative Bacteria: Mechanisms, Transmission, and Novel Intervention Strategies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5156-9243","authenticated-orcid":false,"given":"Shah","family":"Zeb","sequence":"first","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzoo","family":"Nazir","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Fazal","family":"Hameed","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Ikram","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore 54000, Pakistan"},{"name":"Department of Pathology, HBS Medical and Dental College, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Zeeshan","family":"Haider Naqvi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-1840","authenticated-orcid":false,"given":"Muhammad","family":"Shoaib","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-6384","authenticated-orcid":false,"given":"Patrick","family":"Butaye","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6486-9600","authenticated-orcid":false,"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8333-9891","authenticated-orcid":false,"given":"Ruichao","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1330-5925","authenticated-orcid":false,"given":"Xiaoyu","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Taizhou University, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jiph.2016.08.007","article-title":"Antibiotic resistance","volume":"10","author":"Frieri","year":"2017","journal-title":"J. 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