Colistin Resistance Mechanism and Management Strategies of Colistin-Resistant Infections.

The emergence of antibiotic-resistant () is a pressing threat in clinical settings. Colistin is currently a widely used treatment for multidrug-resistant , serving as the last line of defense. However, reports of colistin-resistant strains of have emerged, underscoring the urgent need to develop alternative medications to combat these serious pathogens. To resist colistin, has developed several mechanisms. These include the loss of outer membrane lipopolysaccharides (LPSs) due to mutation of LPS biosynthetic genes, modification of lipid A (a constituent of LPSs) structure through the addition of phosphoethanolamine (PEtN) moieties to the lipid A component by overexpression of chromosomal pmrCAB operon genes and gene, or acquisition of plasmid-encoded genes through horizontal gene transfer. Other resistance mechanisms involve alterations of outer membrane permeability through porins, the expulsion of colistin by efflux pumps, and heteroresistance. In response to the rising threat of colistin-resistant , researchers have developed various treatment strategies, including antibiotic combination therapy, adjuvants to potentiate antibiotic activity, repurposing existing drugs, antimicrobial peptides, nanotechnology, photodynamic therapy, CRISPR/Cas, and phage therapy. While many of these strategies have shown promise in vitro and in vivo, further clinical trials are necessary to ensure their efficacy and widen their clinical applications. Ongoing research is essential for identifying the most effective therapeutic strategies to manage colistin-resistant This review explores the genetic mechanisms underlying colistin resistance and assesses potential treatment options for this challenging pathogen.