Evidence map›Paper›PMID 27141081›Full record

ArticleInfection and immunity2016

Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of rocA Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes.

Luchang Zhu, Randall J Olsen, Nicola Horstmann, Samuel A Shelburne, Jia Fan, Ye Hu, James M Musser

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

16 citing papers in PubMed, 21 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Luchang ZhuCenter for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.
Randall J OlsenCenter for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.
Nicola HorstmannDepartment of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.
Samuel A ShelburneDepartment of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.
Jia FanDepartment of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA.
Ye HuDepartment of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA.
James M MusserCenter for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA jmmusser@houstonmethodist.org.
Houston Methodist · USThe University of Texas MD Anderson Cancer Center · US

Funding

Quantification of Circulating Antigens for Pediatric TB Diagnosis andTreatment MonitoringR01AI122932 · NIAID · METHODIST HOSPITAL RESEARCH INSTITUTE · PI HU, TONY Y. · 2016 to 2019
$1.8M
Real-time Detection of Active TB in HIV Exposed Children on CustomizedNanotrapR01AI113725 · NIAID · METHODIST HOSPITAL RESEARCH INSTITUTE · PI LABAER, JOSHUA · 2015 to 2018
$1.6M
Contribution of catabolite control protein A to group A streptococcal virulenceR01AI089891 · NIAID · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SHELBURNE, SAMUEL A · 2011 to 2015
$1.6M
NIAID NIH HHS R01 AI089891NIAID NIH HHS R01 AI113725NIAID NIH HHS R01 AI122932
6 · The paper itself

Abstract

Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of the rocA gene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes.

Indexed as

Minisatellite RepeatsPolymorphism, GeneticAnimalsBacterial ProteinsBase SequenceDisease Models, AnimalFemaleGene Expression Regulation, BacterialMiceNAD+ NucleosidasePhenotypePhosphorylationSequence DeletionStreptococcal InfectionsStreptococcus pyogenesStreptolysinsBacterial ProteinsNAD+ NucleosidaseRocA protein, Streptococcus pyogenesstreptolysin OStreptolysinsTrans-Activators

Identifiers

PMID27141081
PMCPMC4936349
OpenAlexW2462023030

What OpenQuestion holds

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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.