Evidence map›Paper›PMID 23900173›Full record

ArticlemBio2013

IgG protease Mac/IdeS is not essential for phagocyte resistance or mouse virulence of M1T1 group A Streptococcus.

Cheryl Y M Okumura, Ericka L Anderson, Simon Döhrmann, Dan N Tran, Joshua Olson, Ulrich von Pawel-Rammingen, Victor Nizet

Open access · goldAbstract read
In one paragraph

Article in mBio, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Lysosomal permeabilization by Group AInfection and immunity · 2026
    Article
  2. Review
  3. Article
  4. Immunomodulating Enzymes fromMicroorganisms · 2024
    Review
  5. Review
  6. Article
  7. Playing With Fire: Proinflammatory Virulence Mechanisms of Group AFrontiers in cellular and infection microbiology · 2021
    Review
  8. Review
  9. Article
  10. Article
  11. Group AFrontiers in immunology · 2018
    Article
  12. Neutrophils and Bacterial Immune Evasion.Journal of innate immunity · 2018
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
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 3 institutions in 2 countries.

Cheryl Y M OkumuraDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA. okumura@oxy.edu
Ericka L Anderson
Simon Döhrmann
Dan N Tran
Joshua Olson
Ulrich von Pawel-Rammingen
Victor Nizet
University of California, San Diego · USOccidental College · USUmeå University · SE

Funding

UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
Cathelicidins in Skin ImmunityR01AI052453 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI GALLO, RICHARD L, NIZET, VICTOR · 2002 to 2017
$5.3M
Cathelicidin in Skin ImmunityR37AI052453 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Richard L Gallo, Victor Nizet · 2019 to 2026
$4.6M
GAS Switch from Colonizing Bacterium to Invasive PathogenR01AI077780 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIZET, VICTOR · 2008 to 2019
$3.8M
Proteolysis and Skin AntimicrobialsR01AR052728 · NIAMS · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI GALLO, RICHARD L · 2006 to 2015
$3.3M
NIAID NIH HHS AI077780NIAID NIH HHS R01 AI052453NIAID NIH HHS R01 AI077780NIAID NIH HHS R37 AI052453NIAMS NIH HHS AR052728NIAMS NIH HHS R01 AR052728NIGMS NIH HHS GM068524NIGMS NIH HHS K12 GM068524
6 · The paper itself

Abstract

unlabelledThe Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds. IMPORTANCE: Group A Streptococcus (GAS) causes human infections ranging from strep throat to life-threatening conditions such as flesh-eating disease and toxic shock syndrome. Common disease-associated clones of GAS can cause both mild and severe infections because of a characteristic mutation and subsequent change in the expression of several genes that develops under host immune selection. One of these genes encodes Mac/IdeS, a protease that has been shown to cleave antibodies important to the immune defense system. In this study, we found that while Mac/IdeS is highly expressed in hypervirulent GAS, it does not significantly contribute to the ability of the bacteria to survive white blood cell killing or produce invasive infection in the mouse. These data underscore the importance of correlating studies on virulence factor function with physiologic expression levels and the complexity of streptococcal pathogenesis and contribute to our overall understanding of how GAS causes disease.

Indexed as

AnimalsBacterial ProteinsCell LineCoculture TechniquesDisease Models, AnimalGene DeletionHumansImmunoglobulin GMaleMiceMicrobial ViabilityPhagocytesPhagocytosisProteolysisStreptococcal InfectionsStreptococcus pyogenesBacterial ProteinsImmunoglobulin GMac-1-like protein, StreptococcusVirulence Factors

Identifiers

PMID23900173
PMCPMC3735186
OpenAlexW2166199552

What OpenQuestion holds

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LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

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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.