Evidence map›Paper›PMID 22646689›Full record

ArticleMolecular microbiology2012

Allosteric mutants show that PrfA activation is dispensable for vacuole escape but required for efficient spread and Listeria survival in vivo.

Caroline Deshayes, Magdalena K Bielecka, Robert J Cain, Mariela Scortti, Aitor de las Heras, Zbigniew Pietras, Ben F Luisi, Ricardo Núñez Miguel, José A Vázquez-Boland

Open access · bronzeAbstract read
In one paragraph

Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Long-chain unsaturated free fatty acids reduce the host cell invasion ofFrontiers in cellular and infection microbiology · 2025
    Article
  3. Human Listeriosis.Clinical microbiology reviews · 2023
    Review
  4. mBio · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Chitin Attenuates Expression ofFrontiers in microbiology · 2020
    Article
  9. Review
  10. Regulation ofMicrobiology spectrum · 2019
    Review
  11. Article
  12. Article
  13. Listeriolysin O: from bazooka to Swiss army knife.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. How Listeria monocytogenes organizes its surface for virulence.Frontiers in cellular and infection microbiology · 2014
    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

9 authors at 3 institutions in 2 countries.

Caroline DeshayesCentres for Infectious Diseases and Immunity, Infection & Evolution, University of Edinburgh, Edinburgh, UK.
Magdalena K Bielecka
Robert J Cain
Mariela Scortti
Aitor de las Heras
Zbigniew Pietras
Ben F Luisi
Ricardo Núñez Miguel
José A Vázquez-Boland
Centre for Immunity, Infection and Evolution · GBUniversity of Cambridge · GBUniversidad Complutense de Madrid · ES

Funding

Wellcome Trust 095831Wellcome Trust WT074020MA
6 · The paper itself

Abstract

The transcriptional regulator PrfA controls key virulence determinants of the facultative intracellular pathogen Listeria monocytogenes. PrfA-dependent gene expression is strongly induced within host cells. While the basis of this activation is unknown, the structural homology of PrfA with the cAMP receptor protein (Crp) and the finding of constitutively activated PrfA* mutants suggests it may involve ligand-induced allostery. Here, we report the identification of a solvent-accessible cavity within the PrfA N-terminal domain that may accommodate an activating ligand. The pocket occupies a similar position to the cAMP binding site in Crp but lacks the cyclic nucleotide-anchoring motif and has its entrance on the opposite side of the β-barrel. Site-directed mutations in this pocket impaired intracellular PrfA-dependent gene activation without causing extensive structural/functional alterations to PrfA. Two substitutions, L48F and Y63W, almost completely abolished intracellular virulence gene induction and thus displayed the expected phenotype for allosteric activation-deficient PrfA mutations. Neither PrfA(allo) substitution affected vacuole escape and initial intracellular growth of L. monocytogenes in epithelial cells and macrophages but caused defective cell-to-cell spread and strong attenuation in mice. Our data support the hypothesis that PrfA is allosterically activated during intracellular infection and identify the probable binding site for the effector ligand. They also indicate that PrfA allosteric activation is not required for early intracellular survival but is essential for full Listeria virulence and colonization of host tissues.

Indexed as

MutationTranscriptional ActivationAllosteric RegulationAmino Acid SequenceAmino Acid SubstitutionAnimalsBacterial ProteinsBinding SitesCell LineCyclic AMPFemaleListeria monocytogenesMiceMice, Inbred BALB CModels, MolecularMolecular Sequence DataBacterial ProteinsCyclic AMPPeptide Termination FactorsPrfA protein, Listeria monocytogenes

Identifiers

PMID22646689
PMCPMC3443378
OpenAlexW2116967113

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.