While Tuberculosis (TB) is an ancient disease, it still remains one of top 10 causes of death globally and also a leading cause of death from an infectious agent, exceeding even Human Immunodeficiency Virus (HIV). Worldwide, an estimated 1.7 billion people are infected with Mycobacterium tuberculosis (Mtb). In 2018, an estimated 10.0 million people became ill with TB and almost 1.5 million of TB patients suffered death. Tuberculosis occurs in every part of the world but eight countries with the highest TB burden (India, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa) account for two thirds of the total new TB cases [1]. With early diagnosis and appropriate treatment most of the patients infected with TB can be successfully cured. However, 3.4% of new TB cases and 18% of previously treated cases had Rifampicin-resistant TB (RR-TB) or Multidrug-resistant TB (MDR-TB) which can be treated with significantly lower success rate. According to the latest WHO report the treatment success rate for MDR-TB is 56% globally. In recent years an increase of Extensively Drug-resistant TB (XDR-TB), defined as MDR-TB with additional resistance to at least one of the fluoroquinolones and one of the injectable agents used in MDR-TB treatment

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Propolis is a natural product proved to be efficient against Mycobacterium tuberculosis. Although it is produced by bees, its active alcoholic-aqueous fraction contains plant-derived molecules. To gain some insight into its mechanism of antimycobacterial activity, we studied the metabolic changes in bacterial cells treated with extract of Trigona sp. propolis from Nepal. The detailed metabolomic and transcriptomic analysis performed in this study indicated target points in bacterial cells under propolis extract influence. The profile of lipids forming the outer and middle layer of the mycobacterial cell envelope was not changed by propolis treatment, however, fluctuations in the profiles of amphipathic glycerophospholipids were observed. The enrichment analysis revealed bacterial metabolic pathways affected by Trigona sp. propolis treatment. The early metabolic response involved much more pathways than observed after 48 h of incubation, however, the highest enrichment ratio was observed after 48 h, indicating the long-lasting influence of propolis. The early bacterial response was related to the increased demand for energy and upregulation of molecules involved in the formation of the cell membrane. The transcriptomic analysis confirmed that bacteria also suffered from oxidative stress, which was more pronounced on the second day of exposure. This was the first attempt to explain the action of Nepalese propolis extract against mycobacteria.

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Tuberculosis (TB) is a recurring threat to contemporary civilization. It affects not only those within developing countries, but has also appeared again in places where it was once considered eradicated. TB co-infection in patients infected by HIV is, at the time of writing, the most common cause of death. In the field of searching for new antimycobacterial drug leads, compounds of natural origin still remain a promising source. The review is intended to gather information about natural products (metabolites of plants, fungi, bacteria, and marine sponges) that show activity against mycobacterial enzymes. Here, natural metabolites are presented as being inhibitors/activators of the mycobacterial enzymes involved in mycobacterial growth in vitro (ClpC1, ClpP, MurE ligase, mycothiol S-conjugate amidase, β-ketoacyl-ACP synthase, InhA) and in vivo, as regards the host cell (PtpB). Each enzyme is briefly described so as to generate an understanding of its role in mycobacterial growth and engender a perception of the mechanism of action of the studied natural compounds. Furthermore, after the introduction of the enzyme, its inhibitors are listed and exactly characterized.