Journal article

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

Xukai Jiang, Kai Yang, Bing Yuan, Meiling Han, Yan Zhu, Kade D Roberts, Nitin A Patil, Jingliang Li, Bin Gong, Robert EW Hancock, Tony Velkov, Falk Schreiber, Lushan Wang, Jian Li

Journal of Antimicrobial Chemotherapy | OXFORD UNIV PRESS | Published : 2020


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 penetratio..

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University of Melbourne Researchers


Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health

Awarded by Canadian Institutes for Health Research

Funding Acknowledgements

This research was supported by a research grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI132154). X.J. is a recipient of the 2019 Faculty Bridging Fellowship, Biomedicine Discovery Institute, Monash University. N.A.P. is an Australia National Health and Medical Research Council (NHMRC) ECR Research Fellow. R.E.W.H. is funded by the Canadian Institutes for Health Research FDN-154287 and holds a Canada Research Chair in Health and Genomics and a UBC Killam Professorship. J.L. is an Australia NHMRC Principal Research Fellow.