Molecular Kaleidoscope of Nucleoid-Associated Proteins Regulatory Network and Chromosome Architecture in Mycobacterium Tuberculosis.

Despite significant advancements over the years, Tuberculosis (TB) remains a global threat, especially in low and middle-income countries. The causative agent, Mycobacterium tuberculosis H37Rv, adapts to itsenvironment through Nucleoid-associated proteins (NAPs), which play a crucial role in organizing the bacterial chromosome and regulating gene expression. It is one of the prevalent classes of DNA-binding proteins with dynamic functional characteristics that rearranges the bacterial DNA structure to respond to various stimuli. A notable characteristic of mycobacterial NAPs is their limited sequence similarity with those found in other species, which has posed challenges in their identification. Mycobacterial NAPs, including HupB, Lsr2, EspR, mIHF, Dps, NapA, NapM and MDP2, are involved in essential processes like transcription, growth, chromosomal architecture, antibiotic resistance, and immune evasion. These proteins, often structurally distinct from their counterparts in other species, exhibit dynamic functional characteristics that make them vital for the survival of mycobacteria, especially for M. tuberculosis. However, studying these NAPs presents unique challenges due to their limited sequence conservation. This review aims to explore the diverse roles of NAPs in M. tuberculosis, shed light on the complexities of gene regulation, and discuss the potential for targeting NAPs in future anti-TB therapies.