Inhibition of apoptosis by Rv2456c through Nuclear factor-κB extends the survival of Mycobacterium tuberculosis.


Journal Article

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8+ T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID). One of these FID mutants, FID19, had a transposon insertion in Rv2456c and is important for survival in host cells. The lack of the protein resulted in enhanced caspase-3 mediated apoptosis, which is probably due to an inability to activate nuclear factor-κB. Additionally, FID19 infection enhanced polyfunctional CD8+ T cells and induced a higher frequency of interferon-γ secreting immune cells in a murine model. Taken together, our data suggest that Rv2456c is important for the survival of H37Rv by subduing the innate and ultimately adaptive immune responses of its host by preventing apoptosis of the infected cell. Better understanding of the host-mycobacterial interactions may be beneficial to develop novel drug targets and engineer more efficacious vaccine strains against tuberculosis.

Full Text

Duke Authors

Cited Authors

  • Jurcic Smith, KL; Lee, S

Published Date

  • December 2016

Published In

Volume / Issue

  • 5 / 4

Start / End Page

  • 426 - 436

PubMed ID

  • 27931684

Pubmed Central ID

  • 27931684

Electronic International Standard Serial Number (EISSN)

  • 2212-554X

Digital Object Identifier (DOI)

  • 10.1016/j.ijmyco.2016.06.018


  • eng

Conference Location

  • Netherlands