Overview

• Researchers from Oregon State University, William & Mary, and the NIH integrated lab measurements with NIH NHLBI simulations to build a unified, experimentally validated model.
• The study finds peptides flip across cell membranes to balance their numbers on each side, creating transient pores that cause leakage and disrupt function.
• Potency correlates with pores that are larger, more numerous, and longer-lived, relationships captured in a quantitative equation that predicts membrane disruption.
• Membrane composition and intrinsic defects were identified as key determinants of vulnerability, pointing to ways to tune peptides to preferentially target bacterial cells.
• The peer-reviewed work, published Aug. 29 in PNAS and co-led by Myriam Cotten and NIH’s Richard Pastor, is framed as a step toward therapies for drug-resistant infections, with design and testing of candidates still to come.