exploits host ATM kinase for survival advantage through SecA2 secretome.

() produces inflections in the host signaling networks to create a favorable milieu for survival. The virulent strain, caused double strand breaks (DSBs), whereas the non-virulent strain triggered single-stranded DNA generation. The effectors secreted by SecA2 pathway were essential and adequate for the genesis of DSBs. Accumulation of DSBs mediated through activates ATM-Chk2 pathway of DNA damage response (DDR) signaling, resulting in altered cell cycle. Instead of the classical ATM-Chk2 DDR, gains survival advantage through ATM-Akt signaling cascade. Notably, in vivo infection with led to sustained DSBs and ATM activation during chronic phase of tuberculosis. Addition of ATM inhibitor enhances isoniazid mediated clearance in macrophages as well as in murine infection model, suggesting its utility for host directed adjunct therapy. Collectively, data suggests that DSBs inflicted by SecA2 secretome of provides survival niche through activation of ATM kinase.