Evidence map›Paper›PMID 26635795›Full record

ArticleFrontiers in immunology2015

Streptolysin O Rapidly Impairs Neutrophil Oxidative Burst and Antibacterial Responses to Group A Streptococcus.

Satoshi Uchiyama, Simon Döhrmann, Anjuli M Timmer, Neha Dixit, Mariam Ghochani, Tamara Bhandari, John C Timmer, Kimberly Sprague, Juliane Bubeck-Wardenburg, Scott I Simon and 1 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 95 citations in OpenAlex.

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4 more citing papers are in PubMed but not listed here.

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 4 institutions in 1 country.

Satoshi UchiyamaDepartment of Pediatrics, University of California San Diego , La Jolla, CA , USA.
Simon DöhrmannDepartment of Pediatrics, University of California San Diego , La Jolla, CA , USA.
Anjuli M TimmerDepartment of Pediatrics, University of California San Diego , La Jolla, CA , USA.
Neha DixitDepartment of Biomedical Engineering, University of California Davis , Davis, CA , USA.
Mariam GhochaniDepartment of Biological Sciences, San Diego State University , San Diego, CA , USA.
Tamara BhandariDepartment of Pediatrics, University of California San Diego , La Jolla, CA , USA.
John C TimmerDepartment of Pharmacology, University of California San Diego , La Jolla, CA , USA.
Kimberly SpragueDepartment of Pediatrics, University of California San Diego , La Jolla, CA , USA.
Juliane Bubeck-WardenburgDepartment of Pediatrics, University of Chicago , Chicago, IL , USA.
Scott I SimonDepartment of Biomedical Engineering, University of California Davis , Davis, CA , USA.
Victor NizetDepartment of Pediatrics, University of California San Diego , La Jolla, CA , USA ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , La Jolla, CA , USA.
University of California, San Diego · USUniversity of California, Davis · USSan Diego State University · USUniversity of Chicago · US

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
Outside-in Mechanotransduced Inflammatory TargetsR01AI047294 · NIAID · UNIVERSITY OF CALIFORNIA DAVIS · PI SIMON, SCOTT IRWIN · 1999 to 2021
$7.0M
GAS Switch from Colonizing Bacterium to Invasive PathogenR01AI077780 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIZET, VICTOR · 2008 to 2019
$3.8M
Mechanisms of the M protein in group A Streptococcus virulenceR01AI096837 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PARTHO, NIZET, VICTOR · 2011 to 2015
$2.7M
NIAID NIH HHS R01 AI047294NIAID NIH HHS R01 AI077780NIAID NIH HHS R01 AI096837NIGMS NIH HHS T32 GM007752
6 · The paper itself

Abstract

Group A Streptococcus (GAS) causes a wide range of human infections, ranging from simple pharyngitis to life-threatening necrotizing fasciitis and toxic shock syndrome. A globally disseminated clone of M1T1 GAS has been associated with an increase in severe, invasive GAS infections in recent decades. The secreted GAS pore-forming toxin streptolysin O (SLO), which induces eukaryotic cell lysis in a cholesterol-dependent manner, is highly upregulated in the GAS M1T1 clone during bloodstream dissemination. SLO is known to promote GAS resistance to phagocytic clearance by neutrophils, a critical first element of host defense against invasive bacterial infection. Here, we examine the role of SLO in modulating specific neutrophil functions during their early interaction with GAS. We find that SLO at subcytotoxic concentrations and early time points is necessary and sufficient to suppress neutrophil oxidative burst, in a manner reversed by free cholesterol and anti-SLO blocking antibodies. In addition, SLO at subcytotoxic concentrations blocked neutrophil degranulation, interleukin-8 secretion and responsiveness, and elaboration of DNA-based neutrophil extracellular traps, cumulatively supporting a key role for SLO in GAS resistance to immediate neutrophil killing. A non-toxic SLO derivate elicits protective immunity against lethal GAS challenge in a murine infection model. We conclude that SLO exerts a novel cytotoxic-independent function at early stages of invasive infections (<30 min), contributing to GAS escape from neutrophil clearance.

Indexed as

group A Streptococcusinfectionneutrophil extracellular trapsneutrophilsoxidative burstpore-forming toxinStreptococcus pyogenesstreptolysin O

Identifiers

PMID26635795
PMCPMC4644796
OpenAlexW2172658934

What OpenQuestion holds

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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.