TY - JOUR
T1 - Protein kinase E of Mycobacterium tuberculosis has a role in the nitric oxide stress response and apoptosis in a human macrophage model of infection
AU - Jayakumar, Deepak
AU - Jacobs, William R.
AU - Narayanan, Sujatha
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=38049097940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38049097940&partnerID=8YFLogxK
U2 - 10.1111/j.1462-5822.2007.01049.x
DO - 10.1111/j.1462-5822.2007.01049.x
M3 - Article
C2 - 17892498
AN - SCOPUS:38049097940
SN - 1462-5814
VL - 10
SP - 365
EP - 374
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 2
ER -