Tuberculosis (TB) is a life-threatening infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). Timely diagnosis and effective treatment are essential in the control of TB. Conventional smear microscopy still has low sensitivity and is unable to reveal the drug resistance of this bacterium. The traditional culture-based diagnosis is time-consuming, since usually the results are available after 3–4 weeks. Molecular biology methods fail to differentiate live from dead M. tuberculosis, while diagnostic immunology methods fail to distinguish active from latent TB. In view of these limitations of the existing detection techniques, in addition to the continuous emergence of multidrug-resistant and extensively drug-resistant TB, in recent years there has been an increase in the demand for simple, rapid, accurate and economical point-of-care approaches. This review describes the development, evaluation, and implementation of conventional diagnostic methods for TB and the rapid new approaches for the detection of M. tuberculosis.
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis (Mtb) and is ranked as the second killer infectious disease after COVID-19. Proteasome accessory factor A (PafA) is considered an attractive target because of its low sequence conservation in humans and its role in virulence. In this study, we designed a mutant of Mtb PafA that enabled large-scale purification of active PafA. Using a devised high-throughput screening assay, two PafA inhibitors were discovered. ST1926 inhibited Mtb PafA by binding in the Pup binding groove, but it was less active against Corynebacterium glutamicum PafA because the ST1926-binding residues are not conserved. Bithionol bound to the conserved ATP-binding pocket, thereby, inhibits PafA in an ATP-competitive manner. Both ST1926 and bithionol inhibited the growth of an attenuated Mtb strain (H37Ra) at micromolar concentrations. Our work thus provides new tools for tuberculosis research and a foundation for future PafA-targeted drug development for treating tuberculosis.
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