Phenylethyl Butyrate Enhances the Potency of Second-Line Drugs Against Clinical Isolates of Mycobacterium Tuberculosis

Antimicrob Agents Chemother. 2012 Feb;56(2):1142-5. doi: 10.1128/AAC.05649-11. Epub 2011 Nov 21.

Abstract

Ethionamide (ETH) is a second-line drug for the treatment of tuberculosis. As a prodrug, ETH has to be activated by EthA. ethA is controlled by its repressor EthR. 2-Phenylethyl-butyrate (2-PEB) inhibits EthR binding, enhances expression of EthA, and thereby enhances the growth-inhibitory effects of ethionamide, isoxyl, and thiacetazone in Mycobacterium tuberculosis strains with resistance to ETH due to inhA promoter mutations but not ethA mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / drug effects
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Butyrates / chemistry
  • Butyrates / pharmacology*
  • Drug Resistance, Multiple, Bacterial
  • Drug Synergism
  • Ethionamide / pharmacology*
  • Gene Expression Regulation, Bacterial
  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / isolation & purification
  • Oxidoreductases / genetics
  • Oxygenases / drug effects
  • Oxygenases / genetics
  • Oxygenases / metabolism
  • Phenylthiourea / analogs & derivatives*
  • Phenylthiourea / pharmacology
  • Thioacetazone / pharmacology*

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Butyrates
  • etaA protein, Mycobacterium tuberculosis
  • thiocarlide
  • Phenylthiourea
  • Oxidoreductases
  • Oxygenases
  • InhA protein, Mycobacterium
  • Thioacetazone
  • Ethionamide