Journal article

Effective Strategy Targeting Polymyxin-Resistant Gram-Negative Pathogens: Polymyxin B in Combination with the Selective Serotonin Reuptake Inhibitor Sertraline

Maytham Hussein, Elena K Schneider-Futschik, Olivia KA Paulin, Rafah Allobawi, Simon Crawford, Qi Tony Zhou, Adil Hanif, Mark Baker, Yan Zhu, Jian Li, Tony Velkov

ACS Infectious Diseases | AMER CHEMICAL SOC | Published : 2020

Abstract

This study aimed to investigate synergistic antibacterial activity of polymyxin B in combination with the selective serotonin reuptake inhibitor, sertraline, against the Gram-negative pathogens Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The combination of polymyxin B and sertraline showed synergistic antibacterial activity in checkerboard and static time-kill assays at clinically relevant concentrations against both polymyxin-susceptible and polymyxin-resistant isolates. The potential antimicrobial mode of action of the combination was investigated against P. aeruginosa FADDI-PA024 using untargeted metabolomics alongside scanning and transmission electron mic..

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Grants

Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health


Funding Acknowledgements

J.L. is an Australian National Health and Medical Research Council (NHMRC) Principal Research Fellow, and E.K.S.-F. is an Australian NHMRC Peter Doherty Research Fellow. J.L., T.V., and Q.T.Z. are supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI132681 and AI146160).