Approaches to address Resistance, Drug Discovery, and Vaccine development in Mycobacterium Tuberculosis: Challenges and opportunities

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Background

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis, and it is a single leading cause of significant morbidity and mortality around the world. It is estimated that about one-fourth of the World’s population is infected with TB. TB control programs face serious challenges in developing countries due to high population density that leads to fast transmission of the bacterium and the need of long expensive therapy in order to cure the disease. Conditions such as malnutrition, suppressed immune system, co-infection with HIV and other health conditions contribute significantly to the global spread of TB.

The emergence of multidrug resistant (MDR) M. tuberculosis poses a serious health threat and financial burden to global health agencies. Alarmingly, MDR TB cases in countries such as India are on the rise and estimated to be two to three times higher than in the past few years. The MDR bacterium developed a formidable line of defence against antimicrobials, including target site mutation, drug efflux, alternation in the target sites, and inactivation of drugs by enzymes. There is an urgent need for the development of novel drugs with a different mode of action for effective eradication of MDR M. tuberculosis strains. Combinatorial therapies and drug repurposing are among the latest choices to combat MDR TB.

The present COVID-19 pandemic is another additional root cause, after HIV, in failure to control TB. Due to the increase of immune-compromised patients, the global TB burden is increasing and contributing to a large number of deaths. As for the therapy, the major problems are associated with its long duration and loss of potency and more toxicity of drugs. Failures in TB treatment may lead to the emergence of drug resistant strains and further complicate the therapy.

The current research topic will focus on different aspects of TB and its treatment. First, we consider works that address various mechanisms of drug resistance in M. tuberculosis, especially MDR mechanisms. Furthermore, the topic will include the use of various contemporary techniques such as genomics and proteomics to decipher hidden mechanisms of pathogenicity, drug resistance and identification of new drug target in M. tuberculosis under different physiological condition.

The present research topic will also focus on the development of more potent drugs with novel modes of action, which will be more efficacious against both susceptible and resistant M. tuberculosis strains. These novel drugs are envisaged as contributing to the shortening of TB chemotherapy by targeting persisters and, more importantly, suitable for patients undergoing anti-retroviral therapy.

This research topic will focus on other approaches as well for control and eradication of M. tuberculosis. This may include but not limited to the development of vaccines, for example. We invite contributions from leading experts in the field of TB research. Submissions can be made in any acceptable format (https://www.frontiersin.org/journals/microbiology/sections/antimicrobials-resistance-and-chemotherapy#article-types ).

Keywords: Mycobacterium tuberculosis, Drug resistance, Drug discovery, Genomics and Proteomics, Vaccine development

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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