title: 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: Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
authors: Thomas
authors: T
authors: Grau
authors: Petra
authors: P
authors: Selchow
authors: Marcel
authors: M
authors: Tigges
authors: Reto
authors: R
authors: Burri
authors: Marc
authors: M
authors: Gitzinger
authors: Erik C
authors: EC
authors: Böttger
authors: Martin
authors: M
authors: Fussenegger
authors: Peter
authors: P
authors: Sander
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D005000:Ethionamide / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D010088:Oxidoreductases / Q000235:genetics; D010105:Oxygenases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010670:Phenylthiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D013828:Thioacetazone / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D002087:Butyrates; C414178:etaA protein, Mycobacterium tuberculosis; C100189:thiocarlide; D010670:Phenylthiourea; D010088:Oxidoreductases; D010105:Oxygenases; C085257:InhA protein, Mycobacterium; D013828:Thioacetazone; D005000:Ethionamide