Antibacterial efficacy and membrane mechanism of action of the Serratia -derived non-ionic lipopeptide, serrawettin W2-FL10

Abstract

Antimicrobial resistance is a major public health concern, urgently requiring antibacterial compounds exhibiting low adverse health effects. In this study, a novel antibacterial lipopeptide analog is described, serrawettin W2-FL10 (derived from Serratia marcescens ), with potent activity displayed against Staphylococcus aureus . Mechanistic studies revealed that W2-FL10 targets the cell membrane of S. aureus , causing depolarization and permeabilization because of transmembrane lesions/pores, resulting in the leakage of intracellular components, possible cytosolic uptake of W2-FL10, and ultimately cell death. This study provides the first insight into the mode of action of a non-ionic lipopeptide. The low to moderate cytotoxicity of W2-FL10 also highlights its application as a promising therapeutic agent for the treatment of bacterial infections.