PknE, a serine/threonine protein kinase of Mycobacterium tuberculosis initiates survival crosstalk that also impacts HIV coinfection.

ABSTRACT: Serine threonine protein kinases (STPK) play a major role in the pathogenesis of Mycobacterium tuberculosis. Here, we examined the role of STPK pknE, using a deletion mutant ?pknE in the modulation of intracellular signaling events that favor M. tuberculosis survival. Phosphorylation kinetics of MAPK (p38MAPK, Erk½ and SAPK/JNK) was defective in ?pknE compared to wild-type infected macrophages. This defective signaling dramatically delayed and reduced the phosphorylation kinetics of transcription factors ATF-2 and c-JUN in ?pknE infected macrophages. MAPK inhibitors instead of reducing the phosphorylation in ?pknE infected macrophages, revealed crosstalks with Erk½ signaling influenced by SAPK/JNK and p38 pathways independently. Modulations in intra cellular signaling altered the expression of coreceptors CCR5 and CXCR4 in ?pknE infected macrophages. In conclusion, pknE plays a role in MAPK crosstalks that enables intracellular survival of M. tuberculosis. This survival strategy also impacts HIV/TB coinfection.

SUBMITTER: Parandhaman DK 

PROVIDER: S-EPMC3885422 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature