Metabolomic Description of Ivacaftor Elevating Polymyxin B Mediated Antibacterial Activity in Cystic Fibrosis Pseudomonas aeruginosa
Rafah Allobawi, Drishti P Ghelani, Elena K Schneider-Futschik
ACS Pharmacology & Translational Science | AMER CHEMICAL SOC | Published : 2020
We have demonstrated that ivacaftor displays synergistic antibacterial activity in combination with polymyxin B against polymyxin-resistant Pseudomonas aeruginosa that commonly colonizes the lungs of people with cystic fibrosis (CF). However, the underlying mechanism(s) remain unclear. In the present study, we employed untargeted metabolomics to investigate the synergistic killing mechanism of polymyxin B in combination with ivacaftor against a polymyxin-susceptible P. aeruginosa FADDI-PA111 (polymyxin B MIC = 2 mg/L) and a polymyxin-resistant CF P. aeruginosa FADDI-PA006 (polymyxin B MIC = 8 mg/L). Metabolites were extracted at 3 h after treatments with polymyxin B alone (2 μg/mL for FADDI-..View full abstract
The authors thank Dr Maytham Hussein (University of Melbourne) for technical assistance and Prof Jian Li (Monash University) and A/Prof Tony Velkov (The University of Melbourne) for technical support. E.K.S.-F. is supported by the Peter Phelan Research Award from The Thoracic Society of Australia and New Zealand and by the Australian National Health and Medical Research Council (NHMRC) as a Biomedical Research Fellow.