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 of Pseudomonas aeruginosa, FADDI-PA111 (MIC = 2 mg/liter for both polymyxin B and amikacin), and a polymyxin-resistant Liverpool epidemic strain (LES), LESB58 (the corresponding MIC for both polymyxin B and amikacin is 16 mg/liter). The metabolites were extracted 15 min, 1 h, and 4 h following treatment with polymyxin B alone (2 mg/liter for FADDI-PA111; 4 mg/liter for LESB58), amikacin alone (2 mg/liter), and both in combination and analyzed using liquid chromatography-mass spectrome..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
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.