Deciphering the genes involved in pathogenesis of Mycobacterium tuberculosis

Singh, Ramandeep; Singh, Amit Kumar; Tyagi, Anil K.

doi:10.1016/j.tube.2005.08.015

Cited by 34 publications

(35 citation statements)

References 36 publications

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“…5, A and C) and further shows that PknK-mediated phosphorylation increases the affinity of this transcriptional activator for the promoter it activates. Because VirS is reported to induce transcription from the mym promoter under acidic conditions (44,45), luciferase activity was first assayed in the lysates of M. smegmatis transformants that were exposed to acidic conditions (data not shown). Our results showed that mym promoter has significant basal activity, which is enhanced 2-3-fold by VirS.…”

Section: Discussionmentioning

confidence: 99%

“…The first gene in the mymA operon is mym, which encodes for the Mym protein that is a putative monooxygenase. Knocking out the mym or virS genes resulted in altered cell wall structure (45,46). Because transcription factors are known to be regulated by post-translational modifications such as phosphorylation (47), we decided to investigate the possibility of VirS being a PknK substrate.…”

Section: The Pknk C-terminal Region Ismentioning

confidence: 99%

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The Mycobacterium tuberculosis Protein Kinase K Modulates Activation of Transcription from the Promoter of Mycobacterial Monooxygenase Operon through Phosphorylation of the Transcriptional Regulator VirS

Kumar

Parikh

et al. 2009

Journal of Biological Chemistry

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Mycobacterium tuberculosis encodes for 11 eukaryotic-like serine/threonine protein kinases. Genetic and biochemical studies show that these kinases regulate various cellular processes including cell shape and morphology, glucose and glutamine transport, phagosome-lysosome fusion and the expression, and/or activity of transcription factors. PknK is the largest predicted serine/threonine protein kinase in M. tuberculosis. Here, we have cloned, overexpressed, and purified protein kinase K (PknK) to near homogeneity and show that its ability to phosphorylate proteins is dependent on the invariant lysine (Lys 55 ), and on two conserved threonine residues present in its activation loop. Despite being devoid of any apparent transmembrane domain, PknK is localized to the cell wall fraction, suggesting probable anchoring of the kinase to the cell membrane region. The pknK gene is located in the vicinity of the virS gene, which is known to regulate the expression of the mycobacterial monooxygenase (mymA) operon. We report here for the first time that VirS is in fact a substrate of PknK. In addition, four of the proteins encoded by mymA operon are also found to be substrates of PknK. Results show that VirS is a bona fide substrate of PknK in vivo, and PknK-mediated phosphorylation of VirS increases its affinity for mym promoter DNA. Reporter assays reveal that PknK modulates VirS-mediated stimulation of transcription from the mym promoter. These findings suggest that the expression of mymA operon genes is regulated through PknK-mediated phosphorylation of VirS.

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Section: Discussionmentioning

confidence: 99%

Section: The Pknk C-terminal Region Ismentioning

confidence: 99%

The Mycobacterium tuberculosis Protein Kinase K Modulates Activation of Transcription from the Promoter of Mycobacterial Monooxygenase Operon through Phosphorylation of the Transcriptional Regulator VirS

Kumar

Parikh

et al. 2009

Journal of Biological Chemistry

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“…Some of the "M. tuberculosisspecific" regions identified by this analysis code for known virulence factors or have been proposed to play a role in pathogenesis (Table 3; Supplemental Table 5). These include CDS that produce secondary metabolites such as the sulfolipids, which have been reported to suppress host immune responses Okamoto et al 2006), virS encoding a putative regulator of virulence functions (Singh et al 2005), other regions such as a potential lipid glycosylation locus (Rv0112-Rv0115), and a putative adhesin/transporter locus (Rv0986-Rv0987) (RosasMagallanes et al 2006), as well as the recently reported pilin gene (Rv3312a) (Alteri et al 2007). …”

Section: Evolution Of M Tuberculosis and M Marinum From A Recent Comentioning

confidence: 99%

Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis

Stinear¹,

Seemann²,

Harrison³

et al. 2008

Genome Res.

483

455

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Mycobacterium marinum, a ubiquitous pathogen of fish and amphibia, is a near relative of Mycobacterium tuberculosis, the etiologic agent of tuberculosis in humans. The genome of the M strain of M. marinum comprises a 6,636,827-bp circular chromosome with 5424 CDS, 10 prophages, and a 23-kb mercury-resistance plasmid. Prominent features are the very large number of genes (57) encoding polyketide synthases (PKSs) and nonribosomal peptide synthases (NRPSs) and the most extensive repertoire yet reported of the mycobacteria-restricted PE and PPE proteins, and related-ESX secretion systems. Some of the NRPS genes comprise a novel family and seem to have been acquired horizontally. M. marinum is used widely as a model organism to study M. tuberculosis pathogenesis, and genome comparisons confirmed the close genetic relationship between these two species, as they share 3000 orthologs with an average amino acid identity of 85%. Comparisons with the more distantly related Mycobacterium avium subspecies paratuberculosis and Mycobacterium smegmatis reveal how an ancestral generalist mycobacterium evolved into M. tuberculosis and M. marinum.

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“…Virulence operon in M tuberculosis has been reported [21] and when checked in our operon table, all three genes Rv0986 to Rv0988 of this operon were found to be together. Similarly there are a number of examples like, emb CAB operon [22], ini operon [23], mym A operon [24], kas A operon [25-27] etc for which our predictions were found to be correct.…”

Section: Introductionmentioning

confidence: 77%

MycoperonDB: a database of computationally identified operons and transcriptional units in Mycobacteria

2006

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Background: A key post genomics challenge is to identify how genes in an organism come together and perform physiological functions. An important first step in this direction is to identify transcriptional units, operons and regulons in a genome. Here we implement and report a strategy to computationally identify transcriptional units and operons of mycobacteria and construct a database-MycoperonDB.

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Deciphering the genes involved in pathogenesis of Mycobacterium tuberculosis

Cited by 34 publications

References 36 publications

The Mycobacterium tuberculosis Protein Kinase K Modulates Activation of Transcription from the Promoter of Mycobacterial Monooxygenase Operon through Phosphorylation of the Transcriptional Regulator VirS

The Mycobacterium tuberculosis Protein Kinase K Modulates Activation of Transcription from the Promoter of Mycobacterial Monooxygenase Operon through Phosphorylation of the Transcriptional Regulator VirS

Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis

MycoperonDB: a database of computationally identified operons and transcriptional units in Mycobacteria

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