Unveiling the silent defenders: mycobacterial stress sensors at the forefront to combat tuberculosis.

The global escalation in tuberculosis (TB) cases accompanied by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of(emphasizes the critical requirement for novel potent drugs. Thedemonstrates extraordinary adaptability, thriving in diverse conditions, and always finds itself in win-win situations regardless of whether the environment is favorable or unfavorable; no matter the magnitude of the challenge, it can endure and survive. This review aims to uncover the role of multiple stress sensors ofthat assist bacteria in remaining viable within the host for years against various physiological stresses offered by the host.is an exceptionally triumphant pathogen, primarily due to its adeptness in developing defense mechanisms against stressful situations. The recent advances emphasize the significance ofstress sensors, including chaperones, proteases, transcription factors, riboswitches, inteins, etc., employed in responding to a spectrum of physiological stresses imposed by the host, encompassing surface stress, host immune responses, osmotic stress, oxidative and nitrosative stresses, cell envelope stress, environmental stress, reductive stress, and drug pressure. These sensors act as silent defenders orchestrating adaptive strategies, with limited comprehensive information in current literature, necessitating a focused review. Thestrategies utilizing these stress sensors to mitigate the impact of traumatic conditions demand attention to neutralize this pathogen effectively. Moreover, the intricacies of these stress sensors provide potential targets to design an effective TB drug using structure-based drug design against this formidable global health threat.