Deciphering the Antibacterial Activity and Toxicity of Polymyxins: A Systems Approach

Polymyxins are a last-line class of antibiotics for treating infections caused by Gram-negative 'superbugs'. However, resistance to the polymyxins is increasingly reported and nephrotoxicity is the dose-limiting factor. This project investigated the mechanisms of polymyxin antimicrobial activity and toxicity, as well as the host-pathogen-polymyxin interaction using systems pharmacology. This study provides critical molecular insights for the optimisation of polymyxin use in patients.