Retrograde Trafficking Inhibitor of Shiga Toxins Reduces Morbidity and Mortality of Mice Infected with Enterohemorrhagic Escherichia coli

Antimicrob Agents Chemother. 2015 Aug;59(8):5010-3. doi: 10.1128/AAC.00455-15. Epub 2015 May 18.

Abstract

The most deadly outbreak of Escherichia coli O104:H4 occurred in Europe in 2011. Here, we evaluated the effects of the retrograde trafficking inhibitor Retro-2(cycl) in a murine model of E. coli O104:H4 infection. Systemic treatment with Retro-2(cycl) significantly reduced body weight loss and improved clinical scores and survival rates for O104:H4-infected mice. The present data established that Retro-2(cycl) contributes to the protection of mice against O104:H4 infection and may represent a novel approach to limit Shiga toxin-producing Escherichia coli (STEC)-induced toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology*
  • Benzamides / therapeutic use
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Disease Outbreaks
  • Enterohemorrhagic Escherichia coli / drug effects*
  • Enterohemorrhagic Escherichia coli / genetics
  • Enterohemorrhagic Escherichia coli / pathogenicity
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / epidemiology
  • Europe
  • HeLa Cells
  • Hemolytic-Uremic Syndrome / drug therapy*
  • Hemolytic-Uremic Syndrome / prevention & control
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Shiga Toxin 2 / antagonists & inhibitors*
  • Thiophenes / pharmacology*
  • Thiophenes / therapeutic use
  • Vero Cells

Substances

  • 2-(((5-methyl-2-thienyl)methylene)amino)-N-phenylbenzamide
  • Benzamides
  • Shiga Toxin 2
  • Thiophenes