Evidence map›Paper›PMID 25583521›Full record

ArticleInfection and immunity2015

Streptococcus pyogenes malate degradation pathway links pH regulation and virulence.

Elyse Paluscio, Michael G Caparon

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

17 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. TheJournal of bacteriology · 2025
    Article
  5. Systematic analysis of the glucose-PTS inApplied and environmental microbiology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Group A Streptococcal Virulence: New Lessons.Journal of the Pediatric Infectious Diseases Society · 2019
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. 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

2 authors at 1 institution in 1 country.

Elyse PaluscioDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Michael G CaparonDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA caparon@wusm.wustl.edu.
Washington University in St. Louis · US

Funding

Novel Catabolite Repression Pathway Controls Virulence in Streptococcus pyogenesR01AI070759 · NIAID · WASHINGTON UNIVERSITY · PI CAPARON, MICHAEL G. · 2007 to 2018
$3.4M
ANIMAL SUPPORT SPACE FOR NEUROSCIENCEC06RR015502 · NCRR · WASHINGTON UNIVERSITY · PI CICERO, THEODORE J · 2000 to 2000
$2.0M
NCRR NIH HHS C06 RR015502NIAID NIH HHS AI070759NIAID NIH HHS R01 AI070759
6 · The paper itself

Abstract

The ability of Streptococcus pyogenes to infect different niches within its human host most likely relies on its ability to utilize alternative carbon sources. In examining this question, we discovered that all sequenced S. pyogenes strains possess the genes for the malic enzyme (ME) pathway, which allows malate to be used as a supplemental carbon source for growth. ME is comprised of four genes in two adjacent operons, with the regulatory two-component MaeKR required for expression of genes encoding a malate permease (maeP) and malic enzyme (maeE). Analysis of transcription indicated that expression of maeP and maeE is induced by both malate and low pH, and induction in response to both cues is dependent on the MaeK sensor kinase. Furthermore, both maePE and maeKR are repressed by glucose, which occurs via a CcpA-independent mechanism. Additionally, malate utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI(-) mutant fails to express the ME genes and is unable to utilize malate. Virulence of selected ME mutants was assessed in a murine model of soft tissue infection. MaeP(-), MaeK(-), and MaeR(-) mutants were attenuated for virulence, whereas a MaeE(-) mutant showed enhanced virulence compared to that of the wild type. Taken together, these data show that ME contributes to S. pyogenes' carbon source repertory, that malate utilization is a highly regulated process, and that a single regulator controls ME expression in response to diverse signals. Furthermore, malate uptake and utilization contribute to the adaptive pH response, and ME can influence the outcome of infection.

Indexed as

Gene Expression Regulation, BacterialAnimalsBacterial ProteinsBiological TransportFemaleGene DeletionHydrogen-Ion ConcentrationMalate DehydrogenaseMalatesMiceMice, HairlessMonosaccharide Transport ProteinsMutationOperonOrganic Anion TransportersSoft Tissue InfectionsBacterial ProteinsMalate Dehydrogenasemalate dehydrogenase (decarboxylating)malate permease protein, BacteriaMalatesmalic acidMonosaccharide Transport ProteinsOrganic Anion Transporters

Identifiers

PMID25583521
PMCPMC4333477
OpenAlexW2113839707

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.