scholarly journals A Serine/Threonine Kinase PknL is required For the Persistence of Mycobacterium tuberculosis

2018 ◽  
Vol 6 (2) ◽  
pp. 1-12
Author(s):  
Ahmed Kabir Refaya ◽  
Sujatha Narayanan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

scholarly journals Deletion of the Mycobacterium tuberculosis pknH Gene Confers a Higher Bacillary Load during the Chronic Phase of Infection in BALB/c Mice

2005 ◽  
Vol 187 (16) ◽  
pp. 5751-5760 ◽  
Author(s):  
K. G. Papavinasasundaram ◽  
Bosco Chan ◽  
Ji-Hae Chung ◽  
M. Joseph Colston ◽  
Elaine O. Davis ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Parental Strain ◽  
Chronic Phase ◽  
In Vitro Growth ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Genes Encoding ◽  
Survival Studies ◽  
Mycobacterial Cell Wall

ABSTRACT The role of the serine/threonine kinase PknH in the physiology and virulence of Mycobacterium tuberculosis was assessed by the construction of a pknH deletion mutant. Deletion of the pknH gene did not affect sensitivity to the antimycobacterial drug ethambutol, although it was previously thought to be involved in regulating expression of emb genes encoding arabinosyl transferases, the targets of ethambutol. Nevertheless, transcription analyses revealed that genes associated with mycobacterial cell wall component synthesis, such as emb and ini operons, are downstream substrates of the PknH signaling cascade. In vitro survival studies revealed that a mutant with a deletion of the pknH gene displayed increased resistance to acidified nitrite stress, suggesting that nitric oxide is one of the potential environmental triggers for PknH activation. The effect of pknH deletion on mycobacterial virulence was investigated in BALB/c mice. In this model, the ΔpknH mutant was found to survive and replicate to a higher bacillary load in mouse organs than its parental strain and the pknH-complemented strain. In contrast, another closely related kinase mutant, the ΔpknE mutant, obtained from the same parental strain, was not affected in its virulence phenotype. Infection of THP-1 cells or in vitro growth studies in 7H9 medium did not reveal a significant in vitro growth advantage phenotype for the ΔpknH mutant. In conclusion, we propose that the serine/threonine kinase PknH plays a role in regulating bacillary load in mouse organs to facilitate adaptation to the host environment, possibly by enabling a regulated chronic infection by M. tuberculosis.

scholarly journals The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division

Microbiology ◽  
2006 ◽  
Vol 152 (2) ◽  
pp. 493-504 ◽  
Author(s):  
Arunava Dasgupta ◽  
Pratik Datta ◽  
Manikuntala Kundu ◽  
Joyoti Basu
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Division ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Peptidoglycan Biosynthesis ◽  
Division Site ◽  
Class B ◽  
First Time

A cluster of genes encoded by ORFs Rv0014c–Rv0018c in Mycobacterium tuberculosis encodes candidate cell division proteins RodA and PBPA, a pair of serine/threonine kinases (STPKs), PknA and PknB, and a phosphatase, PstP. The organization of genes encompassing this region is conserved in a large number of mycobacterial species. This study demonstrates that recombinant PBPA of M. tuberculosis binds benzylpenicillin. Knockout of its counterpart in M. smegmatis resulted in hindered growth and defective cell septation. The phenotype of the knockout (PBPA-KO) could be restored to that of the wild-type upon expression of PBPA of M. tuberculosis. PBPA localized to the division site along with newly synthesized peptidoglycan, between segregated nucleoids. In vivo coexpression of PBPA and PknB, in vitro kinase assays and site-specific mutagenesis substantiated the view that PknB phosphorylates PBPA on T362 and T437. A T437A mutant could not complement PBPA-KO. These studies demonstrate for the first time that PBPA, which belongs to a subclass of class B high-molecular-mass PBPs, plays an important role in cell division and cell shape maintenance. Signal transduction mediated by PknB and PstP likely regulates the positioning of this PBP at the septum, thereby regulating septal peptidoglycan biosynthesis.

scholarly journals The Mycobacterium tuberculosis protein serine/threonine kinase PknG is linked to cellular glutamate/glutamine levels and is important for growth in vivo

2004 ◽  
Vol 52 (6) ◽  
pp. 1691-1702 ◽  
Author(s):  
Siobhan Cowley ◽  
Mary Ko ◽  
Neora Pick ◽  
Rayken Chow ◽  
Katrina J. Downing ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

scholarly journals Expression and Characterization of the Mycobacterium tuberculosis Serine/Threonine Protein Kinase PknB

1999 ◽  
Vol 67 (11) ◽  
pp. 5676-5682 ◽  
Author(s):  
Yossef Av-Gay ◽  
Sarwat Jamil ◽  
Steven J. Drews
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Infection Model ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Mitogen Activated Protein

ABSTRACT PknB is a member of the newly discovered eukaryotic-like protein serine/threonine kinase (PSTK) family of proteins. The pknBgene was cloned and expressed in Escherichia coli. The active recombinant protein was purified and shown to be reactive with antiphosphoserine antibodies, as well as with antibodies to the phosphorylated eukaryotic Ser/Thr kinases mitogen-activated protein kinase kinase 3 and 6, P38, and Creb. In vitro kinase assays demonstrated that PknB is a functional kinase that is autophosphorylated on serine/threonine residues and is also able to phosphorylate the peptide substrate myelin basic protein. Analysis ofpknB expression in Mycobacterium tuberculosisindicates the presence of pknB mRNA in (i) organisms grown in vitro in bacteriological media, (ii) a murine macrophage in vitro infection model, and (iii) in vivo alveolar macrophages from a patient with tuberculosis.

scholarly journals Mycobacterium tuberculosis inhibits the NLRP3 inflammasome activation via its phosphokinase PknF

2021 ◽  
Vol 17 (7) ◽  
pp. e1009712
Author(s):  
Shivangi Rastogi ◽  
Sarah Ellinwood ◽  
Jacques Augenstreich ◽  
Katrin D. Mayer-Barber ◽  
Volker Briken
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nlrp3 Inflammasome ◽  
Deletion Mutant ◽  
Adaptor Protein ◽  
Inflammasome Activation ◽  
Serine Threonine Kinase ◽  
Potassium Efflux ◽  
Threonine Kinase ◽  
Nlrp3 Inflammasome Activation ◽  
Infected Cells

Mycobacterium tuberculosis (Mtb) has evolved to evade host innate immunity by interfering with macrophage functions. Interleukin-1β (IL-1β) is secreted by macrophages after the activation of the inflammasome complex and is crucial for host defense against Mtb infections. We have previously shown that Mtb is able to inhibit activation of the AIM2 inflammasome and subsequent pyroptosis. Here we show that Mtb is also able to inhibit host cell NLRP3 inflammasome activation and pyroptosis. We identified the serine/threonine kinase PknF as one protein of Mtb involved in the NLRP3 inflammasome inhibition, since the pknF deletion mutant of Mtb induces increased production of IL-1β in bone marrow-derived macrophages (BMDMs). The increased production of IL-1β was dependent on NLRP3, the adaptor protein ASC and the protease caspase-1, as revealed by studies performed in gene-deficient BMDMs. Additionally, infection of BMDMs with the pknF deletion mutant resulted in increased pyroptosis, while the IL-6 production remained unchanged compared to Mtb-infected cells, suggesting that the mutant did not affect the priming step of inflammasome activation. In contrast, the activation step was affected since potassium efflux, chloride efflux and the generation of reactive oxygen species played a significant role in inflammasome activation and subsequent pyroptosis mediated by the Mtb pknF mutant strain. In conclusion, we reveal here that the serine/threonine kinase PknF of Mtb plays an important role in innate immune evasion through inhibition of the NLRP3 inflammasome.

pknE, a serine/threonine kinase of Mycobacterium tuberculosis modulates multiple apoptotic paradigms

2012 ◽  
Vol 12 (4) ◽  
pp. 737-747 ◽  
Author(s):  
Dinesh Kumar ◽  
Sujatha Narayanan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

scholarly journals The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division

Microbiology ◽  
2015 ◽  
Vol 161 (7) ◽  
pp. 1537-1537
Author(s):  
Arunava Dasgupta ◽  
Joyoti Basu ◽  
Manikuntala Kundu ◽  
Pratik Datta
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Division ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

Protein PknE, a novel transmembrane eukaryotic-like serine/threonine kinase from Mycobacterium tuberculosis

2003 ◽  
Vol 308 (4) ◽  
pp. 820-825 ◽  
Author(s):  
Virginie Molle ◽  
Christine Girard-Blanc ◽  
Laurent Kremer ◽  
Patricia Doublet ◽  
Alain J Cozzone ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

scholarly journals A Serine/threonine kinase PknL , is involved in the adaptive response of Mycobacterium tuberculosis

2016 ◽  
Vol 190 ◽  
pp. 1-11 ◽  
Author(s):  
Ahmed Kabir Refaya ◽  
Divakar Sharma ◽  
Virendra Kumar ◽  
Deepa Bisht ◽  
Sujatha Narayanan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Adaptive Response ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

Beneficial effects of IL-1 cytokine inactivation and the role of the serine/threonine kinase MK-2 in hepatic steatosis in a murine obesity model

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
J Wohlfahrt ◽  
A Fettelschoss ◽  
T Kündig ◽  
H Hermanns ◽  
B Müllhaupt ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Beneficial Effects
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