Journal article
Mechanistic Insights From Global Metabolomics Studies into Synergistic Bactericidal Effect of a Polymyxin B Combination With Tamoxifen Against Cystic Fibrosis MDR Pseudomonas aeruginosa
M Hussein, ML Han, Y Zhu, EK Schneider-Futschik, X Hu, QT Zhou, YW Lin, D Anderson, DJ Creek, D Hoyer, J Li, T Velkov
Computational and Structural Biotechnology Journal | ELSEVIER SCIENCE BV | Published : 2018
Open access
Abstract
Polymyxins are amongst the most important antibiotics in modern medicine, in recent times their clinical utility has been overshadowed by nosocomial outbreaks of polymyxin resistant MDR Gram-negative 'superbugs’. An effective strategy to surmount polymyxin resistance is combination therapy with FDA-approved non-antibiotic drugs. Herein we used untargeted metabolomics to investigate the mechanism(s) of synergy between polymyxin B and the selective estrogen receptor modulator (SERM) tamoxifen against a polymyxin-resistant MDR cystic fibrosis (CF) Pseudomonas aeruginosa FADDI-PA006 isolate (polymyxin B MIC=8 mg/L, it is an MDR polymyxin resistant P. aeruginosa isolated from the lungs of a CF pa..
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Awarded by National Institutes of Health
Funding Acknowledgements
J.L. and T.V. are supported by research grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI132681). J.L. and T.V. are also supported by the Australian National Health and Medical Research Council (NHMRC) as Senior Research and Career Development Level 2 fellows, respectively. 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.