Comparative Metabolomics and Transcriptomics Reveal Multiple Pathways Associated with Polymyxin Killing in Pseudomonas aeruginosa
Mei-Ling Han, Yan Zhu, Darren J Creek, Yu-Wei Lin, Alina D Gutu, Paul Hertzog, Tony Purcell, Hsin-Hui Shen, Samuel M Moskowitz, Tony Velkov, Jian Li
MSYSTEMS | AMER SOC MICROBIOLOGY | Published : 2019
Polymyxins are a last-line therapy against multidrug-resistant Pseudomonas aeruginosa; however, resistance to polymyxins has been increasingly reported. Therefore, understanding the mechanisms of polymyxin activity and resistance is crucial for preserving their clinical usefulness. This study employed comparative metabolomics and transcriptomics to investigate the responses of polymyxin-susceptible P. aeruginosa PAK (polymyxin B MIC, 1 mg/liter) and its polymyxin-resistant pmrB mutant PAKpmrB6 (MIC, 16 mg/liter) to polymyxin B (4, 8, and 128 mg/liter) at 1, 4, and 24 h, respectively. Our results revealed that polymyxin B at 4 mg/liter induced different metabolic and transcriptomic responses ..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
This research was supported by a research grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI111965 [J.L., T.V., and D.J.C.]). J.L. and T.V. are also supported by grant R01 AI132154. M.-L.H. and Y.-W.L. are recipients of the 2018 Faculty Bridging Fellowship, Monash University. J.L. is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow. T.V. and D.J.C. are Australian NHMRC Career Development Research Fellows.