title: 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 ΔpknE in the modulation of intracellular signaling events that favor M. tuberculosis survival. Phosphorylation kinetics of MAPK (p38MAPK, Erk½ and SAPK/JNK) was defective in ΔpknE 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 ΔpknE infected macrophages. MAPK inhibitors instead of reducing the phosphorylation in ΔpknE 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 ΔpknE 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.
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis, Chennai, TamilNadu, India.
authors.forename: Dinesh Kumar
authors.initials: DK
authors.lastname: Parandhaman
authors.affiliation: Department of Clinic Research, HIV division, National Institute for Research in Tuberculosis, Chennai, TamilNadu, India.
authors.forename: Luke Elizabeth
authors.initials: LE
authors.lastname: Hanna
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis, Chennai, TamilNadu, India.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Narayanan
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism; D002460:Cell Line; D060085:Coinfection / Q000382:microbiology* / Q000473:pathology / Q000821:virology*; D015658:HIV Infections / Q000382:microbiology* / Q000473:pathology / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000201:enzymology / Q000382:microbiology / Q000473:pathology / Q000821:virology; D050296:Microbial Viability / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D014376:Tuberculosis / Q000382:microbiology* / Q000473:pathology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D015850:Interleukin-6; D016328:NF-kappa B; D009566:Nitrates; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; C477875:PknE protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases