Evidence map›Paper›PMID 37956179›Full record

ArticlePLoS pathogens2023

Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis.

Thomas J C Sauters, Cullen Roth, Debra Murray, Sheng Sun, Anna Floyd Averette, Chinaemerem U Onyishi, Robin C May, Joseph Heitman, Paul M Magwene

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.0field-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

15 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Towards understanding a potentialOne health (Amsterdam, Netherlands) · 2025
    Article
  5. Article
  6. Unisexual reproduction in the global human fungal pathogenProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Unisexual reproduction in the global human fungal pathogenbioRxiv : the preprint server for biology · 2025
    Article
  9. Tracing the evolution and genomic dynamics of mating-type loci inbioRxiv : the preprint server for biology · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. 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

9 authors at 2 institutions in 2 countries.

Thomas J C SautersDepartment of Biology, Duke University, Durham, North Carolina, United States of America.ORCID 0000-0001-9524-2288
Cullen RothDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Debra MurrayDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Sheng SunDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.
Anna Floyd AveretteDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.
Chinaemerem U OnyishiSchool of Biosciences, College of Life and Environmental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Robin C MaySchool of Biosciences, College of Life and Environmental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Joseph HeitmanDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.
Paul M MagweneDepartment of Biology, Duke University, Durham, North Carolina, United States of America.ORCID 0000-0002-7659-2589
Duke University · USUniversity of Birmingham · GB

Funding

Structure, function, and evolution of the Cryptococcus MAT locusR01AI050113 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 2002 to 2024
$8.5M
ROLE OF CALCINEURIN IN C. NEOFORMANS MATING AND FRUITINGR01AI039115 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 1997 to 2025
$6.7M
The Genetic Basis of Virulence in Cryptococcus NeoformansR01AI133654 · NIAID · DUKE UNIVERSITY · PI JOSEPH HEITMAN, Paul Mitaari Magwene · 2017 to 2026
$4.7M
NIAID NIH HHS R01 AI039115NIAID NIH HHS R01 AI050113NIAID NIH HHS R01 AI133654
6 · The paper itself

Abstract

The "Amoeboid Predator-Fungal Animal Virulence Hypothesis" posits that interactions with environmental phagocytes shape the evolution of virulence traits in fungal pathogens. In this hypothesis, selection to avoid predation by amoeba inadvertently selects for traits that contribute to fungal escape from phagocytic immune cells. Here, we investigate this hypothesis in the human fungal pathogens Cryptococcus neoformans and Cryptococcus deneoformans. Applying quantitative trait locus (QTL) mapping and comparative genomics, we discovered a cross-species QTL region that is responsible for variation in resistance to amoeba predation. In C. neoformans, this same QTL was found to have pleiotropic effects on melanization, an established virulence factor. Through fine mapping and population genomic comparisons, we identified the gene encoding the transcription factor Bzp4 that underlies this pleiotropic QTL and we show that decreased expression of this gene reduces melanization and increases susceptibility to amoeba predation. Despite the joint effects of BZP4 on amoeba resistance and melanin production, we find no relationship between BZP4 genotype and escape from macrophages or virulence in murine models of disease. Our findings provide new perspectives on how microbial ecology shapes the genetic architecture of fungal virulence, and suggests the need for more nuanced models for the evolution of pathogenesis that account for the complexities of both microbe-microbe and microbe-host interactions.

Indexed as

AmoebaCryptococcosisCryptococcus neoformansAnimalsHumansMetagenomicsMicePredatory Behavior

Identifiers

PMID37956179
PMCPMC10681322
OpenAlexW4388624428

What Socratic 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 Socratic graph.