Colistin resistance represents a mounting global health concern, particularly alarming in the face of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial infections. As a polymyxin-class antibiotic, colistin has long served as a critical last-line defence against severe Gram-negative infections caused by pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. However, its increasing and, at times, indiscriminate use has driven the emergence of resistant strains, thereby compromising its clinical utility.Mechanistically, colistin resistance arises from diverse genetic adaptations that alter the bacterial outer membrane, diminishing the drug's binding affinity. Prominent among these are modifications to lipopolysaccharides (LPS), including the incorporation of cationic groups that neutralise the membrane's negative charge, effectively impeding colistin interaction. In addition to chromosomal mutations, resistance is often mediated through horizontal gene transfer-most notably via mobile colistin resistance (mcr) genes-which facilitates rapid dissemination among bacterial populations.To counter this growing threat, innovative therapeutic strategies are urgently needed. These include the development of novel antibiotics with distinct mechanisms of action, synergistic combination regimens (e.g., colistin paired with potentiating agents), and the exploration of alternative modalities such as bacteriophage therapy. Gene-editing technologies like CRISPR-Cas9 also offer a promising frontier for targeting resistance determinants directly at the genetic level.Equally important are robust antimicrobial stewardship programmes and comprehensive surveillance systems to monitor resistance trends and guide rational antibiotic use. Ultimately, overcoming colistin resistance demands a multifaceted and integrative approach-one that merges scientific innovation with global public health initiatives.

Department of Biomedical Science and Technology The School of Biological Sciences Ramakrishna Mission Vivekananda Educational and Research Institute Howrah West Bengal 711202 India

Department of Microbiology Ramakrishna Mission Seva Pratishthan 99 Sarat Bose Road Kolkata West Bengal 700026 India

Department of Microbiology University of Calcutta 35 Ballygunge Circular Road Ballygunge Kolkata 700019 India

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