Evidence map›Paper›PMID 33325565›Full record

ArticleMolecular microbiology2021

Genome-wide analysis of in vivo CcpA binding with and without its key co-factor HPr in the major human pathogen group A Streptococcus.

Sruti DebRoy, Victor Aliaga-Tobar, Gabriel Galvez, Srishtee Arora, Xiaowen Liang, Nicola Horstmann, Vinicius Maracaja-Coutinho, Mauricio Latorre, Magnus Hook, Anthony R Flores and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.8field-weighted citation impact, top 13% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  6. Expanding the genetic toolbox for the obligate human pathogenFrontiers in bioengineering and biotechnology · 2024
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  13. Population Genomics ofmSystems · 2021
    Article
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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

11 authors at 5 institutions in 2 countries.

Sruti DebRoyDepartment of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0001-7328-0443
Victor Aliaga-TobarFacultad de Ciencias Químicas y Farmacéuticas, Advanced Center for Chronic Diseases-ACCDiS, Universidad de Chile, Independencia, Chile.
Gabriel GalvezLaboratorio de Bioingeniería, Instituto de Ciencias de la Ingeniería, Universidad de O'Higgins, Rancagua, Chile.
Srishtee AroraCenter for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
Xiaowen LiangCenter for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
Nicola HorstmannDepartment of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vinicius Maracaja-CoutinhoFacultad de Ciencias Químicas y Farmacéuticas, Advanced Center for Chronic Diseases-ACCDiS, Universidad de Chile, Independencia, Chile.ORCID 0000-0002-8873-9381
Mauricio LatorreLaboratorio de Bioingeniería, Instituto de Ciencias de la Ingeniería, Universidad de O'Higgins, Rancagua, Chile.
Magnus HookCenter for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
Anthony R FloresDivision of Infectious Diseases, Department of Pediatrics, University of Texas Health Science Center McGovern Medical School, Houston, TX, USA.
Samuel A ShelburneDepartment of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0001-9721-263X
Texas A&M Health Science Center · USThe University of Texas MD Anderson Cancer Center · USAdvanced Center for Chronic Diseases · CLUniversity of O'Higgins · CLThe University of Texas Health Science Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Role of response regulator phosphorylation in group A streptococcal pathogenesisR01AI125292 · NIAID · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SHELBURNE, SAMUEL A · 2017 to 2021
$2.0M
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
NCI NIH HHS P30 CA016672NIAID NIH HHS R01 AI089891NIAID NIH HHS R01 AI125292
6 · The paper itself

Abstract

Catabolite control protein A (CcpA) is a master regulator of carbon source utilization and contributes to the virulence of numerous medically important Gram-positive bacteria. Most functional assessments of CcpA, including interaction with its key co-factor HPr, have been performed in nonpathogenic bacteria. In this study we aimed to identify the in vivo DNA binding profile of CcpA and assess the extent to which HPr is required for CcpA-mediated regulation and DNA binding in the major human pathogen group A Streptococcus (GAS). Using a combination RNAseq/ChIP-seq approach, we found that CcpA affects transcript levels of 514 of 1667 GAS genes (31%) whereas direct DNA binding was identified for 105 GAS genes. Three of the directly regulated genes encode the key GAS virulence factors Streptolysin S, PrtS (IL-8 degrading proteinase), and SpeB (cysteine protease). Mutating CcpA Val301 to Ala (strain 2221-CcpA-V301A) abolished interaction between CcpA and HPr and impacted the transcript levels of 205 genes (40%) in the total CcpA regulon. By ChIP-seq analysis, CcpAV301A bound to DNA from 74% of genes bound by wild-type CcpA, but generally with lower affinity. These data delineate the direct CcpA regulon and clarify the HPr-dependent and independent activities of CcpA in a key pathogenic bacterium.

Indexed as

Bacterial ProteinsCarrier ProteinsChromatinDNA, BacterialDNA-Binding ProteinsExotoxinsGene Expression Regulation, BacterialGenome, BacterialProtein BindingRepressor ProteinsRNA-SeqSerine EndopeptidasesStreptococcus pyogenesStreptolysinsVirulenceVirulence FactorsBacterial ProteinsCarrier ProteinsCcpA protein, Streptococcus pyogenesChromatinDNA, BacterialDNA-Binding Proteinserythrogenic toxinExotoxinsRepressor ProteinsSerine Endopeptidasesstreptolysin SStreptolysinsVirulence FactorsChIP-seqHPr-independent CcpA regulationStreptococcus pyogenes

Identifiers

PMID33325565
PMCPMC8359418
OpenAlexW3112602145

What OpenQuestion holds

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LicenceCC BY
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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.