pknE, a serine / threonine kinase of Mycobacterium tuberculosis modulates multiple apoptotic paradigms.
Kumar, D.; Narayanan, S.
Infection, Genetics and Evolution; 2012; 12; 737-747.
Abstract: Mycobacterium tuberculosis , an intracellular pathogen that causes tuberculosis has developed multifactorial mechanisms to evade host signaling responses. Apoptosis, an important innate host immune response that clears the invading pathogen is suppressed by M. tuberculosis to gain persistence. Here, we examined the various apoptotic events suppressed by Protein Kinase E, (pknE) a Serine Threonine Protein Kinase (STPK) of M. tuberculosis in macrophages infected with D pknE, a deletion mutant of pknE vs. the wild type strain H 37 Rv using microarray. The data showed increased expression of genes involved in apoptosis and chemokines with suppressed pro-inflammatory cytokines, co-stimulatory molecules, arginase1 and iNOS. The microarray data was validated using qRT-PCR, PCR array, oligoGE array, arginase assay and/or ELISA. Furthermore, we analyzed the phosphorylation of Akt that promotes cell survival using western blotting. D pknE infected macrophages reduced the phosphorylation of Akt that correlates with the observed apoptotic responses. Experiments performed using exogenous nitrate donor, sodium nitro prusside to demonstrate the role of pknE during nitrate stress showed similar apoptotic responses to that of endogenous nitrate stress in D pknE infected macrophages. Our data confirms the role of pknE in the intra cellular survival of M. tuberculosis by suppressing apoptosis during nitrate stress.
Keywords: pknE; Apoptosis; Arginase; iNOS; Gene expression
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