Activation of the Pro-drug Ethionamide Is Regulated in Mycobacteria *
作者： Alain R. Baulard , Joanna C. Betts , Jean Engohang-Ndong , Selwyn Quan , Ruth A. McAdam
关键词: Stereochemistry 、 Mycobacterium tuberculosis 、 INHA 、 Ethionamide 、 Mutagenesis (molecular biology technique) 、 Isoniazid 、 Molecular biology 、 Open reading frame 、 Activator (genetics) 、 Chemistry 、 Repressor
摘要: The anti-tuberculosis drug ethionamide (ETH), which is a structural analog of isoniazid (INH), known to strongly inhibit mycolic acid synthesis in Mycobacterium tuberculosis. Although several targets have been identified for INH, only speculative information available concerning ETH. Mutations within the promoter and coding region enoyl-acyl carrier protein reductase (InhA) were found confer resistance both drugs, thus leading impression that INH ETH may share common mode action. However, notable distinction between two drugs lies lack cross-resistance clinical isolates. This be attributed part fact pro-drug must activated via KatG, no activation step has yet described. Here we report identification an activator (Rv3854c), termed EthA, was homologous various monooxygenases induced sensitivity when overexpressed mycobacteria. Interestingly, neighboring open reading frame (Rv3855), transcriptional repressors tetRfamily, led overexpressed. In addition, chromosomal inactivation this gene by transposition hypersensitivity. These data suggest Rv3855, EthR, regulates production subsequently activates study opens up new avenues research relating mycobacteria, possibly improved efficacy generation anti-mycobacterial agents.
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