PknE, a Serine/Threonine Protein kinase of Mycobacterium tuberculosis initiates survival crosstalk that also impacts HIV coinfection.

Kumar, D.; Hanna, L.E.; Narayanan, S.

PLoS ONE; 2014; 9; e83541.

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 D 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 D 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 D p knE infected macrophages, revealed cross-talks with Erk½ signaling influenced by SAPK/JNK and p38 pathways independently. Modulations in intracellular signaling altered the expression of co-receptors CCR5 and CXCR4 in D pknE infected macrophages. In conclusion, pknE plays a role in MAPK cross-talks that enables Intracellular survival of M. tuberculosis . This survival strategy also impacts HIV/TB coinfection.

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