Outer Membranes of Polymyxin-Resistant Acinetobacter baumannii with Phosphoethanolamine-Modified Lipid A and Lipopolysaccharide Loss Display Different Atomic-Scale Interactions with Polymyxins.

ABSTRACT: Resistance to the last-line polymyxins is increasingly reported in multidrug-resistant Gram-negative pathogens, including Acinetobacter baumannii, which develops resistance via either lipid A modification (e.g., with phosphoethanolamine [pEtN]) or even lipopolysaccharide (LPS) loss in the outer membrane (OM). Considering these two different mechanisms, quantitative membrane lipidomics data were utilized to develop three OM models representing polymyxin-susceptible and -resistant A. baumannii strains. Through all-atom molecular simulations with enhanced sampling techniques, the effect of lipid A-pEtN modification and LPS loss on the action of colistin (i.e., polymyxin E) was examined for the first time, with a focus on the dynamics and energetics of colistin penetration into t

SUBMITTER: Jiang X 

PROVIDER: S-EPMC7554230 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature