Presentation Information
[C11-05]Synergistic pore formation in Gram-negative bacteria via differential membrane targeting by histones and antimicrobial peptides
*Yonghan Wu1 (1. University of California Irvine (United States of America))
Keywords:
Antimicrobial peptides,Membrane pores,Gram-negative bacteria
Antibiotic resistance in Gram-negative bacteria results in an urgent need for innovative therapeutic approaches. Histones, known primarily for packing DNA, exhibit antimicrobial activity when released extracellularly, yet their specific mechanisms remain unclear. Here, we combined super-resolution stochastic optical reconstruction microscopy (STORM), cryo-electron microscopy (cryo-EM) and mathematical modeling to investigate synergistic interactions between histones and antimicrobial peptides (AMPs). Out images revealed enhanced localization of histones and AMPs on bacterial membranes. Our predictive model, supported by follow-up experiments, demonstrated differential membrane targeting by AMPs and histones, resulting in a maximized synergistic bactericidal effect. Together, this work demonstrates the multifunctional roles of histones and potential ways of overcoming antibiotic resistance through host-derived antimicrobial strategies.