Although worldwide tuberculosis case rates have dropped in the last few years, the disease persists as an immense challenge to global public health. The Mycobacterium tuberculosis complex (MTBC), comprising M. tuberculosis, M. bovis, and M. microti, among others, stands as the most lethal Mycobacterium spp. warranting intensified scrutiny. Research focused on M. microti is particularly important given its status as a zoonotic pathogen capable of moving between animal reservoirs and people. By probing the role of a transglutaminase enzyme in M. microti (MmTG), which is broadly present across Mycobacterium and other organisms, a putative cytotoxic effector has been delineated. MmTG blocks cellular multiplication through the induction of RIPK1 (receptor-interacting serine/threonine-protein kinase 1) phosphorylation, and the Cys159 position of MmTG represents the highly conserved residue tied to its toxic activity. Deciphering MmTG and its homologs can yield a deeper understanding of mycobacterial disease mechanisms and support the design of more efficacious treatment options for mycobacterial infections.
