Sensitivity of Mycobacterium leprae to Telacebec.

The treatment of leprosy is long and complex, benefiting from the development of sterilizing, rapidly-acting drugs. Reductive evolution made Mycobacterium leprae exquisitely sensitive to Telacebec, a phase 2 drug candidate for tuberculosis. The unprecedented potency of Telacebec against M. leprae warrants further validation in clinical trials.

Turbidity-Based MIC Assay and Characterization of Spontaneous Drug Resistant Mutants in Mycobacterium ulcerans.

Generation and characterization of drug resistant mutants is a powerful tool in antimicrobial drug discovery for identification of the molecular target of an investigational drug candidate. The method is relatively simple to be conducted in a classical microbiology laboratory. Its value has been augmented by the employment of next generation sequencing techniques to characterize single-nucleotide polymorphisms associated with drug resistance. Determination of the frequency of emergence of resistance to drug candidates also provides insights into their usefulness for clinical application. In addition to the generation of drug resistant mutants, we describe a direct method to determine the minimum inhibitory concentration of a drug candidate against Mycobacterium ulcerans.

Determination of Bioenergetic Parameters in Mycobacterium ulcerans.

The oxidative phosphorylation (OxPhos) pathway has emerged as an attractive pathway for the development of anti-mycobacterial drugs. The OxPhos pathway is essential for ATP resynthesis and maintenance of the electrochemical transmembrane gradient. The bioenergetic parameters of the pathway such as oxygen consumption rate and ATP levels are quantifiable using current technology. Measuring these parameters are useful tools to gauge rapidly the impact of drug candidates on their capacity to inhibit the OxPhos pathway in Mycobacterium ulcerans.