Journal article

Structure-Interaction Relationship of Polymyxins with the Membrane of Human Kidney Proximal Tubular Cells

Xukai Jiang, Shuo Zhang, Mohammad AK Azad, Kade D Roberts, Lin Wan, Bin Gong, Kai Yang, Bing Yuan, Hemayet Uddin, Jingliang Li, Philip E Thompson, Tony Velkov, Jing Fu, Lushan Wang, Jian Li

ACS Infectious Diseases | AMER CHEMICAL SOC | Published : 2020


Multidrug-resistant Gram-negative bacteria are a serious global threat to human health. Polymyxins are increasingly used in patients as a last-line therapy to treat infections caused by these life-threatening 'superbugs'. Unfortunately, polymyxin-induced nephrotoxicity is the major dose-limiting factor and understanding its mechanism is crucial for the development of novel, safer polymyxins. Here, we undertook the first all-atom molecular dynamics simulations of the interaction between four naturally occurring polymyxins A1, B1, M1 and colistin A (representative structural variations of the polymyxin core structure) and the membrane of human kidney proximal tubular cells. All polymyxins inse..

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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 National Key Research and Development Project

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). The simulations were performed on the supercomputer cluster MASSIVE 3 at Monash University (Australia) and the HPC Cloud Platform (National Key Research and Development Project, 2016YFB0201702) at Shandong University (China). XKJ is the recipient of a 2019 Faculty Bridging Fellowship, Monash University. JL is an Australia National Health and Medical Research Council (NHMRC) Principal Research Fellow. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.