Evidence map›Paper›PMID 26714274›Full record

ArticleMolecular microbiology2016

Structural and functional analysis of RopB: a major virulence regulator in Streptococcus pyogenes.

Nishanth Makthal, Maire Gavagan, Hackwon Do, Randall J Olsen, James M Musser, Muthiah Kumaraswami

Open access · hybridAbstract read
In one paragraph

Article in Molecular microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.6field-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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. RopB represses the transcription ofLife science alliance · 2023
    Article
  3. Streptococcal peptides and their roles in host-microbe interactions.Frontiers in cellular and infection microbiology · 2023
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. A novel chemical inducer ofThe Journal of biological chemistry · 2018
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. 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

6 authors at 1 institution in 1 country.

Nishanth MakthalCenter for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
Maire GavaganCenter for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
Hackwon DoCenter for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, 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, TX, 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, TX, USA.
Muthiah KumaraswamiCenter for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
Houston Methodist · US

Funding

Molecular mechanism of virulence regulation in Streptococcus pyogenesR01AI109096 · NIAID · METHODIST HOSPITAL RESEARCH INSTITUTE · PI KUMARASWAMI, MUTHIAH · 2015 to 2019
$2.0M
Mechanism of streptococcus virulence regulation by bacterial peptide signalsR21AI103708 · NIAID · METHODIST HOSPITAL RESEARCH INSTITUTE · PI KUMARASWAMI, MUTHIAH · 2013 to 2014
$419k
NIAID NIH HHS 1R01AI109096NIAID NIH HHS 1R21AI103708-01NIAID NIH HHS R01 AI109096NIAID NIH HHS R21 AI103708
6 · The paper itself

Abstract

Group A Streptococcus (GAS) is an exclusive human pathogen that causes significant disease burden. Global regulator RopB of GAS controls the expression of several major virulence factors including secreted protease SpeB during high cell density. However, the molecular mechanism for RopB-dependent speB expression remains unclear. To understand the mechanism of transcription activation by RopB, we determined the crystal structure of the C-terminal domain of RopB. RopB-CTD has the TPR motif, a signature motif involved in protein-peptide interactions and shares significant structural homology with the quorum sensing RRNPP family regulators. Characterization of the high cell density-specific cell-free growth medium demonstrated the presence of a low molecular weight proteinaceous secreted factor that upregulates RopB-dependent speB expression. Together, these results suggest that RopB and its cognate peptide signals constitute an intercellular signalling machinery that controls the virulence gene expression in concert with population density. Structure-guided mutational analyses of RopB dimer interface demonstrated that single alanine substitutions at this critical interface significantly altered RopB-dependent speB expression and attenuated GAS virulence. Results presented here suggested that a properly aligned RopB dimer interface is important for GAS pathogenesis and highlighted the dimerization interactions as a plausible therapeutic target for the development of novel antimicrobials.

Indexed as

Amino Acid SequenceBacterial ProteinsCrystallography, X-RayExotoxinsGene Expression Regulation, BacterialProtein Sorting SignalsProtein Structure, SecondaryStreptococcal InfectionsStreptococcus pyogenesStructure-Activity RelationshipTranscription, GeneticVirulenceVirulence FactorsBacterial ProteinsExotoxinsProtein Sorting SignalsRopB protein, Rhizobium leguminosarumVirulence Factors

Identifiers

PMID26714274
PMCPMC4794775
OpenAlexW2232192708

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.