Biophysical Society Thematic Meeting | Stockholm 2022

Physical and Quantitative Approaches to Overcome Antibiotic Resistance

Poster Abstracts

5-POS Board 5 COMPUTATIONAL INVESTIGATIONS OF THE DUAL MECHANISMS OF ACTION OF ANTIMICROBIAL LENTHIPEPTIDES Prem P. Chapagain 1,2 ; Rudramani Pokhrel 1 ; Nisha Bhattarai 1 ; Prabin Baral 1 ; Bernard Gerstman 1,2 ; Jae Park 3 ; Martin Handfield 3 ; 1 Florida International University, Physics, Miami, FL, USA 2 Florida International University, Biomolecular Sciences Institute, Miami, FL, USA 3 Oragenics Inc., Alachua, FL, USA The alarming rise in antibacterial resistant infections in recent years due to the widespread use of antibiotics has underscored a dire need for the development of new antibiotics utilizing novel modes of action. Due to their diverse bioactivities, the post-translationally modified peptides known as lanthipeptides are promising candidates against drug-resistant bacteria. The modes of action of lanthipeptides include interference with cell wall synthesis by binding to lipid II and creating pores in bacterial membranes. We use atomic-scale molecular dynamics computational studies to compare the lipid II binding abilities as well as their transmembrane behaviors of five different lanthipeptides that are commonly used in antimicrobial research. These include, nisin, MU1140, gallidermin, NVB302, and NAI107. Among the five peptides investigated, nisin is found to be the most efficient at forming water channels through a membrane, whereas gallidermin and MU1140 are found to be better at binding the lipid II molecules. This study provides insights into the dual mechanisms of the action of lantibiotic peptides and can facilitate the design and development of novel lanthipeptides.

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