Deletion of the Trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole

Antimicrob Agents Chemother. 2007 Feb;51(2):755-8. doi: 10.1128/AAC.01360-06. Epub 2006 Dec 4.

Abstract

It has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. However, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Deletion
  • Genes, Protozoan
  • Nifurtimox / pharmacology*
  • Nitroimidazoles / pharmacokinetics*
  • Parasitic Sensitivity Tests
  • Superoxide Dismutase / genetics*
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosoma brucei brucei / enzymology
  • Trypanosoma brucei brucei / genetics*

Substances

  • Nitroimidazoles
  • Superoxide Dismutase
  • Nifurtimox
  • benzonidazole