Harnessing Bacteriophages to Overcome Tuberculosis: Challenges and Advancements.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a significant global health challenge, leading to a substantial number of deaths each year. The emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), presents a serious threat to TB control efforts. Phage therapy uses phages like mycobacteriophages, which infect species including M. tuberculosis, as a potential treatment for TB. Some mycobacteriophages, such as D29, TM4, and DS6A, have shown promise in preclinical studies by effectively targeting drug-resistant TB strains. The role of the lytic enzyme system involving LysA and LysB genes dedicatedly targets the specific Mycobacterium species' mycolic acid and peptidoglycan layer in due course of action. Besides this, the review also suggests the possibility of an efficient delivery system in the mammalian cell microenvironment. The new strategies also involve the CRISPR-Cas system as a molecular tool to facilitate the generation of mycobacteriophage variants with desired functional attributes. However, phage therapy faces shortcomings such as identifying specific phage-bacterial strains, regulatory compliances, and addressing potential immune responses. Although, the optimal delivery to the infection site, determining the ideal dosage, and addressing concerns about bacterial resistance are under critical consideration. Ongoing efforts focused on overcoming these limitations and translating promising preclinical results into clinical applications. Keywords: Multidrug-resistant Antibiotics, Mycobacterium tuberculosis, Mycobacterium smegmatis, Mycobacteriophages, CRISPR-Cas, Phage delivery system