Colistin Resistance in Bacteria: Current Updates on Mechanism of Action and Combating Strategies

The rapid development of colistin-resistant bacteria is the biggest global health issue since colistin is referred to as a 'last-hope resource' against life-threatening infections caused by GNB (Gram-negative bacteria). Injudicious and excessive colistin application in clinical, agricultural and veterinary practices, as well as plasmid-mediated horizontal gene transfer and chromosomal mutation, commonly contribute to colistin resistance. The coexistence of the mcr-1 gene with mcr variants, other intrinsic genes and other mechanisms might provide additional resistance strength against colistin. To prevent the emergence of colistin-resistant strains and preserve the therapeutic efficacy of existing antibiotics, we must expand our deep understanding of colistin-resistant strains at the molecular level. This critical review discusses the mechanism of action, various bacterial resistance mechanisms, the presence of mcr genes in bacterial plasmids, hetero-resistance, biofilm formation, the horizontal transfer or dispersion of colistin-resistant genes and combating strategies. Our synthesis underscores the need for strategically aligning mechanistic knowledge with practical therapeutic solutions to combat escalating colistin resistance and inform future medical decision-making and research planning.