Otilonium bromide boosts antimicrobial activities of colistin against Gram-negative pathogens and their persisters

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

3 Scopus Citations
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Author(s)

  • Chen Xu
  • Kaichao Chen
  • Ping Zeng
  • Edward Wai Chi Chan

Detail(s)

Original languageEnglish
Article number613
Journal / PublicationCommunications Biology
Volume5
Online published21 Jun 2022
Publication statusPublished - 2022

Link(s)

Abstract

Colistin is the last-line antibiotic against Gram-negative pathogens. Here we identify an FDA-approved drug, Otilonium bromide (Ob), which restores the activity of colistin against colistin-resistant Gram-negative bacteria in vitro and in a mouse infection model. Ob also reduces the colistin dosage required for effective treatment of infections caused by colistin-susceptible bacteria, thereby reducing the toxicity of the drug regimen. Furthermore, Ob acts synergistically with colistin in eradicating multidrug-tolerant persisters of Gram-negative bacteria in vitro. Functional studies and microscopy assays confirm that the synergistic antimicrobial effect exhibited by the Ob and colistin involves permeabilizing the bacterial cell membrane, dissipating proton motive force and suppressing efflux pumps, resulting in membrane damages, cytosol leakage and eventually bacterial cell death. Our findings suggest that Ob is a colistin adjuvant which can restore the clinical value of colistin in combating life-threatening, multidrug resistant Gram-negative pathogens.

Research Area(s)

  • Animals, Anti-Bacterial Agents/pharmacology, Colistin/pharmacology, Drug Resistance, Multiple, Bacterial, Drug Synergism, Gram-Negative Bacteria/drug effects, Mice, Microbial Sensitivity Tests, Quaternary Ammonium Compounds/pharmacology

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