Metabolomics Study of the Synergistic Killing of Polymyxin B in Combination with Amikacin against Polymyxin-Susceptible and -Resistant Pseudomonas aeruginosa

Abstract

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 ..