Targeting of the Brucella suis virulence factor histidinol dehydrogenase by histidinol analogues results in inhibition of intramacrophagic multiplication of the pathogen

Antimicrob Agents Chemother. 2007 Oct;51(10):3752-5. doi: 10.1128/AAC.00572-07. Epub 2007 Aug 13.

Abstract

Brucella suis histidinol dehydrogenase (HDH) can be efficiently targeted by substrate analogues. The growth of this pathogen in minimal medium was inhibited and the multiplication in human macrophages was totally abolished in the presence of the drugs. These effects have been shown to be correlated with the previously described inhibition of Brucella HDH activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / antagonists & inhibitors*
  • Brucella suis / drug effects*
  • Brucella suis / growth & development
  • Brucella suis / pathogenicity
  • Brucellosis / microbiology
  • Cell Line
  • Culture Media
  • Enzyme Inhibitors / pharmacology*
  • Histidine / pharmacology
  • Histidinol / analogs & derivatives*
  • Histidinol / pharmacology*
  • Humans
  • Ketones / pharmacology
  • Macrophages / drug effects
  • Macrophages / microbiology*
  • Structure-Activity Relationship
  • Virulence Factors / antagonists & inhibitors*

Substances

  • Culture Media
  • Enzyme Inhibitors
  • Ketones
  • Virulence Factors
  • Histidine
  • Histidinol
  • Alcohol Oxidoreductases
  • histidinol dehydrogenase