title: Protein kinase E of Mycobacterium tuberculosis has a role in the nitric oxide stress response and apoptosis in a human macrophage model of infection.
abstract: Mycobacterium tuberculosis, an intracellular pathogen, inhibits macrophage apoptosis to support survival and replication inside the host cell. We provide evidence that the functional serine/threonine kinase, PknE, is important for survival of M. tuberculosis that enhances macrophage viability by inhibiting apoptosis. A promoter of PknE identified in this study was shown to respond to nitric oxide stress. Deletion of pknE in virulent M. tuberculosis, H37Rv, resulted in a strain that has increased resistance to nitric oxide donors and increased sensitivity to reducing agents. The deletion mutant created by specialized transduction induced enhanced apoptosis while inhibiting necrosis. The pknE mutant also modifies the innate immune response as shown by the marked decline in the pro-inflammatory cytokines in a macrophage model of infection. These findings suggest a novel mechanism, by which PknE senses nitric oxide stress and prevents apoptosis by interfering with host signalling pathways.
authors: Department of Immunology, Tuberculosis Research Centre (ICMR), Chetput, Chennai-600031, India.
authors: Deepak
authors: D
authors: Jayakumar
authors: William R
authors: WR
authors: Jacobs
authors: Sujatha
authors: S
authors: Narayanan
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D017353:Gene Deletion; D006801:Humans; D008264:Macrophages; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D009336:Necrosis / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D016207:Cytokines; D009569:Nitric Oxide; C477875:PknE protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases