In the Quest for New Horizons: Evaluating Novel Therapeutic Approaches for Tuberculosis Treatment

Tuberculosis (TB) in humans, caused by Mycobacterium tuberculosis, is a significant global health concern, resulting in high disease burden and mortality each year which together make it the world’s topmost infectious killer. The emergence of multidrug-resistant tuberculosis (MDR-TB) in recent decades has further exacerbated the present situation and warrants an urgent need to develop and investigate innovative treatment regimes. This study aims to assess the therapeutic potential of newly identified drug candidates, namely Bedaquiline, Delamanid, and Linezolid, in treating MDR-TB. We adopted a consolidated and integrated approach encompassing a thorough literature review, empirical experimental studies, multiple sequence alignments, and computational analyses, towards an in-depth analysis of the gene targets of these drugs and their efficacy in M. tuberculosis. Our findings indicate the significant potential of these drugs for tackling and treating drug-resistant TB, especially when synergized with prevailing first-line and second-line drugs. Notably, our results show a stark difference in the proteins and enzymes targeted by these drugs in mycobacteria versus those of the representative gut bacteria, providing a rationale for the minimal or mild side effects while administering these drugs in TB patients. Despite current infectious disease crises, including the COVID-19 disease, developing novel antibiotic treatments remains paramount against several serious bacterial pathogens. Our research offers a renewed perspective on enhancing therapeutic interventions by delving into drug combinatorial therapy against deadly infections, akin to those employed against drug-resistant tuberculosis. This research was supported by CUNY Research Foundation, NIH Bridges grant 5T34GM137858-04 (NIH NIGMS), and CUNY Research Scholars Program (CRSP). Dr. Richa Gupta served as the Principal Investigator and Research Mentor, and is the recipient of the Cycle 48 PSC-CUNY research award and Community College Research Grant (CCRG); Selassie Mawuko, Aminata Traore, and Bibi-Sakeena Khemraj were supported by the NIH Bridges Undergraduate Research Scholarship; and Anna Steto was supported by the CRSP Undergraduate Research Scholarship. This research was supported by CUNY Research Foundation, NIH Bridges grant 5T34GM137858-04 (NIH NIGMS), and CUNY Research Scholars Program (CRSP). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.