Phenylethyl butyrate enhances the potency of second-line drugs against clinical isolates of Mycobacterium tuberculosis.

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.

• Authors: Thomas Grau, Petra Selchow, Marcel Tigges, Reto Burri, Marc Gitzinger, Erik C Böttger, Martin Fussenegger, Peter Sander
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 56 Issue 2 Pg. 1142-5 (Feb 2012) ISSN: 1098-6596 [Electronic] United States
• PMID: 22106218 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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