Bacteria have evolved numerous and diverse pathways to produce and secrete bacteriocins as weapons of bacterial warfare. These molecules are processed inside the cell and then transported across the bacterial membrane for secretion. We recently discovered the TMcins, a distinct class of bacteriocins found across gram-positive bacteria that contain a transmembrane helix and kill target bacteria by forming large pores. Using a Staphylococcus aureus strain that naturally produces TMcin, we show that TMcin production occurs in the cell membrane and reveal how bacteria process a membrane-spanning peptide in a lipid environment. This work expands our understanding of how bacteria produce antimicrobials and provides a model for discovering other membrane-localized natural products.

The bacterial cell cycle is an ensemble of integrated pathways that coordinates cell growth and division. Although these pathways contain a suite of promising antimicrobial targets, their functional o...