The dry antibiotic development pipeline coupled with the emergence of multi-drug resistant Gram-negative 'superbugs' has driven the revival of the polymyxin lipopeptide antibiotics. Understanding the mode of action of antibiotics is an important precursor for optimizing their use and development. This chapter provides a concise treatise of the current knowledge-based on the primary mode of action of polymyxins as well as recent developments in understanding of bacterial cell responses and secondary modes of action.
Keywords: Free radical; LPS; Outer membrane remodelling; Polymyxin; Type II NADH-quinone oxidoreductase.