Metabolomics Study of the Synergistic Killing of Polymyxin B in Combination with Amikacin against Polymyxin-Susceptible and -Resistant Pseudomonas aeruginosa
Maytham Hussein, Mei-Ling Han, Yan Zhu, Qi Zhou, Yu-Wei Lin, Robert EW Hancock, Daniel Hoyer, Darren J Creek, Jian Li, Tony Velkov
Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2020
In the present study, we employed untargeted metabolomics to investigate the synergistic killing mechanism of polymyxin B in combination with an aminoglycoside, amikacin against a polymyxin-susceptible isolate P. aeruginosa FADDI-PA111 (MICs = 2 mg/L for both polymyxin B and amikacin) and a polymyxin-resistant Liverpool Epidemic Strain LESB58 (the corresponding MIC for both polymyxin B and amikacin is 16 mg/L ). The metabolites were extracted at 15 min, 1 and 4 h following treatment with polymyxin B alone (2 mg/L for FADDI-PA111; 4 mg/L for LESB58), amikacin alone (2 mg/L) and in combination; and analyzed using LC-MS. At 15 min and 1 h, polymyxin B alone induced significant perturbations in ..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health
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 principal 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.