Evidence map›Paper›PMID 22243650›Full record

ArticleBMC microbiology2012

Role of Mycobacterium tuberculosis pknD in the pathogenesis of central nervous system tuberculosis.

Nicholas A Be, William R Bishai, Sanjay K Jain

Open access · goldAbstract read
In one paragraph

Article in BMC microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 87 citations in OpenAlex.

  1. Trial
  2. Host- and pathogen-related determinants of pulmonaryEuropean respiratory review : an official journal of the European Respiratory Society · 2026
    Review
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  11. Review
  12. Bacterial meningitis in Africa.Frontiers in neurology · 2023
    Review
  13. Multi-Omics ofProteomes · 2022
    Article
  14. International journal of molecular sciences · 2022
    Article
  15. Review
  16. Proteomes · 2021
    Article
  17. Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Nicholas A BeCenter for Tuberculosis Research, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, Maryland 21287, USA.
William R Bishai
Sanjay K Jain
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

Novel imaging biomarkers to address fundamental controversies in TB pathogenesisDP2OD006492 · OD · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2009 to 2014
$2.9M
SUPERANTIGENS AND THE MHC--STRUCTURE/FUNCTIONR01AI030036 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI COOK, RICHARD G · 1991 to 2000
$343k
Diagnosis of active TB in HIV infected and uninfected young children in IndiaR03HD061059 · NICHD · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2009 to 2010
$132k
Howard Hughes Medical InstituteNIAID NIH HHS AI30036NICHD NIH HHS HD061059NIH HHS DP2 OD006492NIH HHS OD006492
6 · The paper itself

Abstract

backgroundCentral nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct Mycobacterium tuberculosis strains with central nervous system disease, the microbial virulence factors required have not been described previously.

resultsWe screened 398 unique M. tuberculosis mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found M. tuberculosis pknD (Rv0931c) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that pknD is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. M. tuberculosis pknD encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the M. tuberculosis PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.

conclusionsOur findings demonstrate a novel in vivo role for M. tuberculosis pknD and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.

Indexed as

AnimalsBacterial LoadBrainFlow CytometryGuinea PigsMicroscopy, ConfocalMycobacterium tuberculosisProtein KinasesSurvival AnalysisTuberculosis, Central Nervous SystemVirulence FactorsPknD protein, Nostoc sp. PCC 7120Protein KinasesVirulence Factors

Identifiers

PMID22243650
PMCPMC3322341
OpenAlexW2164675361

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.