Journal article
Polymyxins Bind to the Cell Surface of Unculturable Acinetobacter baumannii and Cause Unique Dependent Resistance
Y Zhu, J Lu, ML Han, X Jiang, MAK Azad, NA Patil, YW Lin, J Zhao, Y Hu, HH Yu, K Chen, JD Boyce, RA Dunstan, T Lithgow, CK Barlow, W Li, EK Schneider-Futschik, J Wang, B Gong, B Sommer Show all
Advanced Science | WILEY | Published : 2020
Abstract
Multidrug-resistant Acinetobacter baumannii is a top-priority pathogen globally and polymyxins are a last-line therapy. Polymyxin dependence in A. baumannii (i.e., nonculturable on agar without polymyxins) is a unique and highly-resistant phenotype with a significant potential to cause treatment failure in patients. The present study discovers that a polymyxin-dependent A. baumannii strain possesses mutations in both lpxC (lipopolysaccharide biosynthesis) and katG (reactive oxygen species scavenging) genes. Correlative multiomics analyses show a significantly remodeled cell envelope and remarkably abundant phosphatidylglycerol in the outer membrane (OM). Molecular dynamics simulations and qu..
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Awarded by National Institutes of Health
Funding Acknowledgements
\The authors thank Australian National Computation Infrastructure and High-Performance Computation Cloud Platform at Shandong University Jinan, China) for providing computational resources. They also thank Monash Micromon andGenewiz for DNA and RNA sequencing, Advanced Microscopy Facility at Bio21 Institute for SEM, and Monash Proteomics and Metabolomics Facility for providing LC-MS service. J.L. and T.V. are supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI132154 and AI132681). 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. N.A.P. and E.K.S. are Australian National Health andMedical Research Council (NHMRC) Early Career Fellows. T.L. is an Australian Laureate Fellow supported by the Australian Research Council. D.J.C. and T.V. are Australian NHMRC Career Development Research Fellows. J.L. is an Australian NHMRC Principal Research Fellow.