IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria

Sci Rep. 2021 Feb 3;11(1):2942. doi: 10.1038/s41598-021-82377-z.

Abstract

Sepsis is caused by organ dysfunction initiated by an unrestrained host immune response to infection. The emergence of antibiotic-resistant bacteria has rapidly increased in the last decades and has stimulated a firm research platform to combat infections caused by antibiotic-resistant bacteria that cannot be eradicated with conventional antibiotics. Strategies like epigenetic regulators such as lysine demethylase (Kdm) has received attention as a new target. Thus, we sought to investigate the epigenetic mechanisms in sepsis pathophysiology with the aim of discovering new concepts for treatment. A transcriptome analysis of dendritic cells during their inflammatory state identified Kdm as a critical molecule in sepsis regulation. Next, 8-hydroxyquinoline-5-carboxylic acid (IOX1) ability to control endotoxemia induced by Lipopolysaccharide and bacterial sepsis was demonstrated. IOX1 has been shown to regulate endotoxemia and sepsis caused by Escherichia coli and carbapenem-resistant Acinetobacter baumannii and has also contributed to the suppression of multidrug-resistant bacterial growth through the inhibition of DNA Gyrase. These findings show that IOX1 could be a component agent against bacterial sepsis by functioning as a broad-spectrum antibiotic with dual effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter Infections / immunology
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • DNA Gyrase / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Escherichia coli / drug effects
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / microbiology
  • Female
  • Histone Demethylases / antagonists & inhibitors
  • Histone Demethylases / metabolism
  • Humans
  • Hydroxyquinolines / pharmacology*
  • Hydroxyquinolines / therapeutic use
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Sepsis / microbiology

Substances

  • Anti-Bacterial Agents
  • Hydroxyquinolines
  • Histone Demethylases
  • DNA Gyrase
  • 5-carboxy-8-hydroxyquinoline