The microbiome-derived antibacterial lugdunin acts as a cation ionophore in synergy with host peptides.

ABSTRACT: Lugdunin is a microbiome-derived antibacterial agent with good activity against Gram-positive pathogens in vitro and in animal models of nose colonization and skin infection. We have previously shown that lugdunin depletes bacterial energy resources by dissipating the membrane potential of Staphylococcus aureus. Here, we explored the mechanism of action of lugdunin in more detail and show that lugdunin quickly depolarizes cytoplasmic membranes of different bacterial species and acidifies the cytoplasm of S. aureus within minutes due to protonophore activity. Varying the salt species and concentrations in buffers revealed that not only protons are transported, and we demonstrate the binding of the monovalent cations K⁺, Na⁺, and Li⁺ to l

SUBMITTER: Berscheid A 

PROVIDER: S-EPMC11389392 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature