Tuberculosis virulence gene inhibits apoptosis of infected host cells
The infection-induced suicide of host cells (apoptosis) following invasion by intracellular pathogens is an ancient defense mechanism observed in multicellular organisms of both the animal and plant kingdoms. It is therefore not surprising that persistent pathogens of viral, bacterial, and protozoal origin have evolved to inhibit the induction of host cell death. Mycobacterium tuberculosis, the etiological agent of tuberculosis, has latently infected about one third of the world’s population and can persist for decades in the lungs of infected, asymptomatic individuals.
The survival and persistence of M. tuberculosis depends on its capacity to manipulate multiple host defense pathways, including the ability to actively inhibit the death by apoptosis of infected host cells. The genetic basis for this anti-apoptotic activity and its implication for mycobacterial virulence have not previously been determined. Using a novel gain-of-function genetic screen, a recent paper demonstrated that inhibition of infection-induced apoptosis of macrophages is controlled by multiple genetic loci in M. tuberculosis. Characterization of one of these loci in detail revealed that the anti-apoptosis activity was attributable to the type I NADH-dehydrogenase of M. tuberculosis, and was mainly due to the subunit of this multicomponent complex encoded by the nuoG gene. A mutant of M. tuberculosis in which nuoG was deleted triggered a marked increase in apoptosis by infected macrophages, and subsequent analysis of this mutant in the mouse tuberculosis model provided direct evidence for a causal link between the capacity to inhibit apoptosis and bacterial virulence. The discovery of anti-apoptosis genes in M. tuberculosis could provide a powerful approach to the generation of better attenuated vaccine strains, and may also identify a new group of drug targets for improved chemotherapy.
Well, can this anti-apoptotic gene be exploited to yield cellular immortality or to make a cell population like the HeLa cells?
[...] Tuberculosis virulence gene inhibits apoptosis of infected host cells [...]
[...] Tuberculosis virulence gene inhibits apoptosis of infected host cells [...]