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Eastern countries are a major source of medicinal plants, which set up a rich source of ethnopharmacologically known medicines used in the treatment of various diseases. These traditional medicines have been known as complementary, alternative, or nonconventional therapy across globe for ages. Tuberculosis (TB) poses a huge global burden and leads to maximum number of deaths due to an infectious agent. Treatment of TB using Directly Observed Treatment Short‐course (DOTS) therapy comprises multiple antibiotics is quite lengthy and causes serious side‐effects in different organs. The length of the TB treatment leads to withdrawal from the patients, which paves the way for the emergence of drug resistance in the bacterial population. These concerns related to therapy need serious and immediate interventions. Traditional medicines using phytochemicals has shown to provide tremendous potential in TB treatment, mainly in the eradication of Mycobacterium tuberculosis (M.tb), increasing natural immunity, and managing the side effects of anti‐TB drugs. This review describes the antituberculosis potential of selected ethnopharmacologically important phytochemicals as potential immune‐modulator and as an adjunct‐therapy in TB. This review will be a useful reference for researchers working on ethnopharmacology and will open the door for the discovery of novel agents as an adjunct‐therapy to tuberculosis., The different modes of action of phytochemicals in adjunct therapy for the treatment of TB.

Epigenetics involves changing the gene function without any change in the sequence of the genes. In the case of tuberculosis (TB) infections, the bacilli, Mycobacterium tuberculosis (M.tb), uses epigenetics as a tool to protect itself from the host immune system. TB is a deadly disease-causing maximum death per year due to a single infectious agent. In the case of TB, there is an urgent need for novel host-directed therapies which can effectively target the survival and long-term persistence of the bacteria without developing drug resistance in the bacterial strains while also reducing the duration and toxicity associated with the mainstream anti-TB drugs. Recent studies have suggested that TB infection has a significant effect on the host epigenome thereby manipulating the host immune response in the favor of the pathogen. M.tb alters the activation status of key genes involved in the immune response against TB to promote its survival and subvert the antibacterial strategies of the host. These changes are reversible and can be exploited to design very efficient host-directed therapies to fight against TB. This review has been written with the purpose of discussing the role of epigenetic changes in TB pathogenesis and the therapeutic approaches involving epigenetics, which can be utilized for targeting the pathogen.

Tuberculosis (TB) remains a major infectious disease worldwide. TB treatment displays a biphasic bacterial clearance, in which the majority of bacteria clear within the first month of treatment, but residual bacteria remain nonresponsive to treatment and eventually may become resistant. Here, we have shown that Mycobacterium tuberculosis was taken up by mesenchymal stem cells (MSCs), where it established dormancy and became highly nonresponsive to isoniazid, a major constituent of directly observed treatment short course (DOTS). Dormant M. tuberculosis induced quiescence in MSCs and promoted their long-term survival. Unlike macrophages, where M. tuberculosis resides in early-phagosomal compartments, in MSCs the majority of bacilli were found in the cytosol, where they promoted rapid lipid synthesis, hiding within lipid droplets. Inhibition of lipid synthesis prevented dormancy and sensitized the organisms to isoniazid. Thus, we have established that M. tuberculosis gains dormancy in MSCs, which serve as a long-term natural reservoir of dormant M. tuberculosis. Interestingly, in the murine model of TB, induction of autophagy eliminated M. tuberculosis from MSCs, and consequently, the addition of rapamycin to an isoniazid treatment regimen successfully attained sterile clearance and prevented disease reactivation.

Tuberculosis (TB) is an infectious disease caused by an obligate intracellular pathogen, Mycobacterium tuberculosis (M.tb) and is responsible for the maximum number of deaths due to a single infectious agent. Current therapy for TB, Directly Observed Treatment Short-course (DOTS) comprises multiple antibiotics administered in combination for 6 months, which eliminates the bacteria and prevents the emergence of drug-resistance in patients if followed as prescribed. However, due to various limitations viz., severe toxicity, low efficacy and long duration; patients struggle to comply with the prescribed therapy, which leads to the development of drug resistance (DR). The emergence of resistance to various front-line anti-TB drugs urgently require the introduction of new TB drugs, to cure DR patients and to shorten the treatment course for both drug-susceptible and resistant populations of bacteria. However, the development of a novel drug regimen involving 2-3 new and effective drugs will require approximately 20-30 years and huge expenditure, as seen during the discovery of bedaquiline and delamanid. These limitations make the field of drug-repurposing indispensable and repurposing of pre-existing drugs licensed for other diseases has tremendous scope in anti-DR-TB therapy. These repurposed drugs target multiple pathways, thus reducing the risk of development of drug resistance. In this review, we have discussed some of the repurposed drugs that have shown very promising results against TB. The list includes sulfonamides, sulfanilamide, sulfadiazine, clofazimine, linezolid, amoxicillin/clavulanic acid, carbapenems, metformin, verapamil, fluoroquinolones, statins and NSAIDs and their mechanism of action with special emphasis on their immunomodulatory effects on the host to attain both host-directed and pathogen-targeted therapy. We have also focused on the studies involving the synergistic effect of these drugs with existing TB drugs in order to translate their potential as adjunct therapies against TB.

Tuberculosis (TB) is the leading cause of death worldwide due to an infectious disease, causing around 1.6 million deaths each year. This situation has become more complicated by the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) and HIV-TB co-infection, which has significantly worsened TB prognosis and treatment. Despite years of intensive research, Bacille Calmette-Guerin (BCG) remains the only licensed vaccine and has variable efficacy. It provides protection against childhood TB but is not effective in adult pulmonary TB. As a result of intense research in understanding TB vaccinology, there are many new vaccine candidates in clinical development and many more in pre-clinical trials which aim either to replace or boost BCG vaccine. This review discusses the history of BCG vaccine development and summarizes limitations of the current vaccine strategy and recent advances in improving BCG immunization along with other new vaccines in clinical trials which are promising candidates for the future tuberculosis vaccinology program.

Ethnopharmacological relevance The emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains has severely hampered global efforts towards tuberculosis (TB) eradication. The internationally accepted therapy “Directly Observed Treatment Short-course (DOTS)” is lengthy, and incorporates risks for the generation of drug-resistant M.tb variants. Multiple and extremely drug-resistant (MDR and XDR) variants of TB are now widespread throughout the globe, and totally drug-resistant (TDR) strains have appeared. Therefore, new classes of antibiotics are urgently needed to combat these deadly organisms. Historically, garlic is known to kill mycobacterial strains, and its active compound, allicin, kills various microorganisms. Here we have shown that allicin not only reduced the bacterial burden in the lungs of mice infected with Mycobacterium tuberculosis (M.tb), but also induces strong anti-tubercular immunity. Materials and methods In the present study, the anti-mycobacterial and immunomodulatory activity of garlic extract and its pure constituent allicin were demonstrated based on several in vitro and in vivo experiments in murine model of tuberculosis. Furthermore, the validation of study was done by immunoblots showing the modulation of MAPK and SAPK/JNK signaling by allicin in macrophages. Results Here, we report that allicin/garlic extract exhibits strong anti-mycobacterial responses in vitro and in vivo against drug-sensitive, MDR and XDR strains of TB. In addition to direct killing, allicin also induced pro-inflammatory cytokines in macrophages. Moreover, allicin/garlic extract treatment in murine models of infection resulted in induction of strong protective Th1 response, leading to drastic reduction in mycobacterial burden. These results indicated that allicin/garlic extract has both antibacterial and immunomodulatory activity. Furthermore, garlic extract reversed the immune dampening effects of frontline anti-TB drugs. Conclusion Allicin/garlic extract alone or as an adjunct to classical antibiotics holds great promise for treatment of drug-sensitive as well as drug-resistant TB. These results warrant further study and validation of allicin for treatment of TB.