Redox biology underlying the efficacy and toxicity of colistin as a last-resort antibiotic.

The increasing prevalence of multidrug-resistant Gram-negative bacteria has reinforced the clinical importance of last-resort antibiotics such as colistin. Their antibacterial efficacy has made them indispensable for treating life-threatening infections, yet their clinical use is constrained by substantial toxicity. Increasing evidence indicates that redox biology may influence both the antibacterial activity and host toxicity of colistin through distinct biological processes. Reactive oxygen species contribute to bacterial killing while simultaneously promoting mitochondrial dysfunction, oxidative stress, inflammation, and tubular cell death within the kidney. This mini review summarizes current knowledge on the redox mechanisms underlying the antibacterial activity and host toxicity of last-resort antibiotics, with particular emphasis on colistin-induced nephrotoxicity. We discuss experimental and clinical evidence supporting host-directed redox modulation as a strategy to mitigate renal injury, highlighting the limitations that have hindered successful clinical translation. Finally, we examine emerging opportunities, including biomarker-guided strategies and mitochondria-targeted interventions, that may facilitate the development of safer therapeutic approaches while preserving the antibacterial efficacy of colistin.