Mycobacterium tuberculosis as a resilient foe in the mechanisms of colonisation, pathogenesis and host immune responses serves as a prerequisite for the development of potential mangrove plant-derived anti-TB drugs

Mycobacterium tuberculosis (MTB) is a highly adaptive pathogen that emerged as a devastating and mortality-related disease agent. The limited efficacy of the Mycobacterium bovis BCG vaccine, antibiotics and intensive treatment to prevent mortality have piqued researchers' interest in host-pathogen interactions. Besides the emergence of multi-drug resistant TB as a drawback, the host immune responses could be successfully subverted and exploited by the MTB-host pathogenesis during the early stages of innate immunity. Factors contributing to mycobacterial pathogenesis are concomitant and multifactorial, including virulence factors such as adhesins, toxins and enzymes that drive the progression of MTB infection. Initially, alveolar macrophage (AM), which has been considered to restrain bacterial growth, facilitates the spread of disease through interactions with MTB. The progression to bacterial replication and systemic infection before the initiation of cell-mediated immunity (CMI) indicates a delay in the activation of adaptive immunity, which is crucial. The findings are supported by the bacterial multiplication and dissemination in the infected alveolar macrophage in animal models. On the other hand, mangrove plants have revealed a structural diversity and a plethora of compounds responsible for antibacterial, antifungal and antiviral activities. These may serve as potential bioactive compounds for anti-TB drugs. In this review, we discuss mycobacterial colonisation, tissue invasion and host inflammatory responses that lead to the pathogenesis of MTB, along with the potential bioactive compounds for alternative plant-derived anti-TB drugs. The mechanistic insights provide significant discoveries on the limitations of immunity, offering important strategies for developing immunomodulating drugs.