Evidence map›Paper›PMID 23297387›Full record

ArticleInfection and immunity2013

Genome-wide identification of genes required for fitness of group A Streptococcus in human blood.

Yoann Le Breton, Pragnesh Mistry, Kayla M Valdes, Jeffrey Quigley, Nikhil Kumar, Hervé Tettelin, Kevin S McIver

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
11.1field-weighted citation impact, top 1% 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

74 citing papers in PubMed, 115 citations in OpenAlex.

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  13. Two chronically misdiagnosed patients infected withFrontiers in cellular and infection microbiology · 2022
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  14. Article
  15. The Evolution of Fluoroquinolone Resistance inInternational journal of molecular sciences · 2021
    Article
  16. Article
  17. Pathogens (Basel, Switzerland) · 2021
    Review
  18. AmBio · 2021
    Article
  19. Article
  20. Article

14 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

7 authors at 2 institutions in 1 country.

Yoann Le BretonDepartment of Cell Biology & Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, USA.
Pragnesh Mistry
Kayla M Valdes
Jeffrey Quigley
Nikhil Kumar
Hervé Tettelin
Kevin S McIver
University of Maryland, College Park · USUniversity of Maryland, Baltimore · US

Funding

PRD-Containing Virulence Regulators of Pathogenic StreptococciR01AI047928 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI MCIVER, KEVIN S. · 2001 to 2023
$6.5M
Global Genetic Analysis of the Mga Virulence RegulonF31AI100576 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI VALDES, KAYLA M · 2012 to 2015
$170k
SEROTYPE ANALYSIS AND CHARACTERIZATION OF ROTAVIRUSES FROM MALAYSIAZ01AI000576 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI RASOOL, N · 1990 to 1992
–
NIAID NIH HHS AI00576NIAID NIH HHS AI47928NIAID NIH HHS F31 AI100576NIAID NIH HHS R01 AI047928
6 · The paper itself

Abstract

The group A streptococcus (GAS) is a strict human pathogen responsible for a wide spectrum of diseases. Although GAS genome sequences are available, functional genomic analyses have been limited. We developed a mariner-based transposon, osKaR, designed to perform Transposon-Site Hybridization (TraSH) in GAS and successfully tested its use in several invasive serotypes. A complex osKaR mutant library in M1T1 GAS strain 5448 was subjected to negative selection in human blood to identify genes important for GAS fitness in this clinically relevant environment. Mutants underrepresented after growth in blood (output pool) compared to growth in rich media (input pool) were identified using DNA microarray hybridization of transposon-specific tags en masse. Using blood from three different donors, we identified 81 genes that met our criteria for reduced fitness in blood from at least two individuals. Genes known to play a role in survival of GAS in blood were found, including those encoding the virulence regulator Mga (mga), the peroxide response regulator PerR (perR), and the RofA-like regulator Ralp-3 (ralp3). We also identified genes previously reported for their contribution to sepsis in other pathogens, such as de novo nucleotide synthesis (purD, purA, pyrB, carA, carB, guaB), sugar metabolism (scrB, fruA), zinc uptake (adcC), and transcriptional regulation (cpsY). To validate our findings, independent mutants with mutations in 10 different genes identified in our screen were confirmed to be defective for survival in blood bactericidal assays. Overall, this work represents the first use of TraSH in GAS to identify potential virulence genes.

Indexed as

BloodChromosome MappingChromosomes, BacterialGene Expression Regulation, BacterialGenetic FitnessGenome, BacterialHemolysin ProteinsHumansMutagenesis, InsertionalMutationStreptococcus pyogenesHemolysin Proteins

Identifiers

PMID23297387
PMCPMC3584890
OpenAlexW2056147938

What OpenQuestion holds

Textmetadata
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.