Fast-growing, non-infectious and intracellularly surviving drug-resistant Mycobacterium aurum: a model for high-throughput antituberculosis drug screening

摘要: Objectives: Enoyl acyl-carrier-protein reductase (InhA), the primary endogenous target for isoniazid and ethionamide, is crucial to type-II fatty acid biosynthesis (FAS-II). The objectives of this study were first generate InhA mutants Mycobacterium aurum, secondly characterize InhA-mediated ethionamide resistance mechanisms across those finally investigate interaction with enzymes in FAS-II pathway M. aurum. Methods: Spontaneous generated by overdose limited broth dilution, while genetically modified sense‐antisense DNA technology was used. Southern hybridization immunoprecipitation both used identify homologue latter method further compare level expression aurum that corresponding mutants. Isoniazid/ethionamide susceptibility modulation examined vitro ex vivo using a resazurin assay as well cfu counting. In addition, circular dichroism bacterial twohybrid system exploited other pathway. Results :A tuberculosis detected Susceptibility isoniazid/ethionamide significantly altered simultaneously overexpressed spontaneous interacts vivo. Conclusion: Close resemblance action on between supports use fast-growing intracellularly surviving drug-resistant substitute highly virulent, extremely slow-growing strains early stage antituberculosis inhibitor screening.