Multifaceted DosR proteins of Mycobacterium tuberculosis: emerging roles for tuberculosis control

Tuberculosis (TB) is an infectious disease induced by Mycobacterium tuberculosis (Mtb). TB continues to pose a significant global health concern owing to limitation in vaccination effectiveness, diagnostic accuracy, and extended treatment regimen that foster drug resistance. Mtb dormancy is a non-replicative, metabolically modified condition that enables the bacterium to survive inside host macrophages, resulting in latent TB infection for years. This survival strategy is activated by stressors like hypoxia and low pH, resulting in phenotypic drug resistance and the capacity to reactivate when the host's immune system is compromised. The Dormancy Survival Regulon (DosR regulon), a set of 48 genes, is specifically activated in response to hypoxia and several stressors associated with latent infection. These genes are crucial for maintaining redox balance, controlling ATP levels, and altering bacterial metabolism to ensure the extended life of Mtb during dormancy. This review study assesses the implications of the DosR regulon in the pathophysiology of Mtb, recognising it as a potential target for novel diagnostics, vaccines, and therapies. These proteins possess a vast array of antigenic epitopes, including HspX, Rv2004c, Rv0569, Rv1733c, Rv2627c, and Rv2628, which have considerable immunogenic potential in preclinical studies as recombinant BCG or subunit vaccines. These antigens are only expressed during the latent phase, making them possible indicators for differentiating between latent and active TB, as well as improving serodiagnosis. Therapeutic suppression of DosR proteins may obstruct the development of bacterial dormancy, possibly decreasing treatment duration and recurrence rates.