Evidence map›Paper›PMID 22402035›Full record

ArticleThe Journal of infectious diseases2012

The Mycobacterium tuberculosis stress response factor SigH is required for bacterial burden as well as immunopathology in primate lungs.

Smriti Mehra, Nadia A Golden, Kerstan Stuckey, Peter J Didier, Lara A Doyle, Kasi E Russell-Lodrigue, Chie Sugimoto, Atsuhiko Hasegawa, Satheesh K Sivasubramani, Chad J Roy and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

57 citing papers in PubMed, 82 citations in OpenAlex.

  1. Review
  2. Journal of bacteriology · 2026
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  3. Neutrophil kinetics ofFrontiers in cellular and infection microbiology · 2026
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  7. Model systems to studyFrontiers in cellular and infection microbiology · 2025
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  15. Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  16. Article
  17. Article
  18. Article
  19. Transcriptional Response ofFrontiers in microbiology · 2021
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 6 countries.

Smriti MehraDivision of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, LA 70433, USA.
Nadia A Golden
Kerstan Stuckey
Peter J Didier
Lara A Doyle
Kasi E Russell-Lodrigue
Chie Sugimoto
Atsuhiko Hasegawa
Satheesh K Sivasubramani
Chad J Roy
Xavier Alvarez
Marcelo J Kuroda
James L Blanchard
Andrew A Lackner
Deepak Kaushal
Rostov Research Institute of Microbiology and Parasitology · RUUniversity of Veterinary Medicine · HULaboratoire d'ethnologie et de sociologie comparative · FRTulane University · USOregon National Primate Research Center · USSwiss Institute of Comparative Law · CH

Funding

Tulane NPRC SPF Sheltered Outdoor Enclosure ExpansionP51OD011104 · OD · TULANE UNIVERSITY OF LOUISIANA · PI L Lee HAMM · 2012 to 2026
$142.4M
ZCM:A NOVEL BROAD-SPECTRUM MICROBICIDE FOR SEXUALLY TRANSMITTED INFECTIONSP51RR000164 · NCRR · TULANE UNIVERSITY OF LOUISIANA · PI VEAZEY, RONALD S. · 1985 to 2011
$100.1M
TNF AND MCP-1 IN RETROVIRUS-INDUCED BRAIN DISEASEP20RR020159 · NCRR · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI PAHAR, BAPI · 2004 to 2011
$16.1M
Macrophages in the pathogenesis of AIDSR01AI097059 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI KURODA, MARCELO J · 2012 to 2016
$4.0M
Genetic Requirements for the survival of Tubercle Bacilli in Nonhuman PrimatesR01AI089323 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI KAUSHAL, DEEPAK · 2010 to 2014
$3.2M
Transcriptomics of Tuberculosis Latency and Reactivation in PrimatesR01HL106790 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI KAUSHAL, DEEPAK · 2010 to 2013
$3.1M
Role of miRNA in lung damage during TB and TB/AIDS Co-infectionR21AI091457 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI KAUSHAL, DEEPAK · 2010 to 2011
$452k
Macaque model of TB/AIDS co-infection via natural routes of exposureR21RR026006 · NCRR · TULANE UNIVERSITY OF LOUISIANA · PI KAUSHAL, DEEPAK · 2009 to 2010
$452k
NCRR NIH HHS P20 RR020159NCRR NIH HHS P51 RR000164NCRR NIH HHS R21 RR026006NCRR NIH HHS RR000164NCRR NIH HHS RR020159NCRR NIH HHS RR026006NHLBI NIH HHS HL106790NHLBI NIH HHS R01 HL106790NIAID NIH HHS AI089323NIAID NIH HHS AI091457NIAID NIH HHS R01 AI089323NIAID NIH HHS R01 AI097059NIAID NIH HHS R21 AI091457NIH HHS P51 OD011104
6 · The paper itself

Abstract

backgroundSigma H (sigH) is a major Mycobacterium tuberculosis (Mtb) stress response factor. It is induced in response to heat, oxidative stress, cell wall damage, and hypoxia. Infection of macrophages with the Δ-sigH mutant generates more potent innate immune response than does infection with Mtb. The mutant is attenuated for pathology in mice.

methodsWe used a nonhuman primate (NHP) model of acute tuberculosis, to better understand the phenotype of the Δ-sigH mutant in vivo. NHPs were infected with high doses of Mtb or the mutant, and the progression of tuberculosis was analyzed in both groups using clinical, pathological, microbiological, and immunological parameters.

resultsAnimals exposed to Mtb rapidly progressed to acute pulmonary tuberculosis as indicated by worsening clinical correlates, high lung bacterial burden, and granulomatous immunopathology. All the animals rapidly succumbed to tuberculosis. On the other hand, the NHPs exposed to the Mtb:Δ-sigH mutant did not exhibit acute tuberculosis, instead showing significantly blunted disease. These NHPs survived the entire duration of the study.

conclusionsThe Mtb:Δ-sigH mutant is completely attenuated for bacterial burden as well as immunopathology in NHPs. SigH and its regulon are required for complete virulence in primates. Further studies are needed to identify the molecular mechanism of this attenuation.

Indexed as

AnimalsBacterial ProteinsGene Expression ProfilingGene Expression Regulation, BacterialGranulomaImmunohistochemistryLungMacaca mulattaMycobacterium tuberculosisSigma FactorTuberculosis, PulmonaryBacterial ProteinsSigH protein, bacteriaSigma Factor

Identifiers

PMID22402035
PMCPMC3308902
OpenAlexW2101534380

What OpenQuestion holds

Textmetadata
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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.