Molecular dynamics simulations informed by membrane lipidomics reveal the structure-interaction relationship of polymyxins with the lipid A-based outer membrane of Acinetobacter baumannii.

ABSTRACT:

Background

MDR bacteria represent an urgent threat to human health globally. Polymyxins are a last-line therapy against life-threatening Gram-negative 'superbugs', including Acinetobacter baumannii. Polymyxins exert antimicrobial activity primarily via permeabilizing the bacterial outer membrane (OM); however, the mechanism of interaction between polymyxins and the OM remains unclear at the atomic level.

Methods

We constructed a lipid A-based OM model of A. baumannii using quantitative membrane lipidomics data and employed all-atom molecular dynamics simulations with umbrella sampling techniques to elucidate the structure-interaction relationship and thermodynamics governing the penetration of polymyxins [B1 and E1 (i.e. colistin A) representing the two clinically used polym

SUBMITTER: Jiang X 

PROVIDER: S-EPMC7662177 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature