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

Publication ,  Journal Article
Sauters, TJC; Roth, C; Murray, D; Sun, S; Floyd Averette, A; Onyishi, CU; May, RC; Heitman, J; Magwene, PM
Published in: PLoS Pathog
November 2023

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.

Duke Scholars

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

November 2023

Volume

19

Issue

11

Start / End Page

e1011763

Location

United States

Related Subject Headings

  • Virology
  • Predatory Behavior
  • Mice
  • Metagenomics
  • Humans
  • Cryptococcus neoformans
  • Cryptococcosis
  • Animals
  • Amoeba
  • 3207 Medical microbiology
 

Citation

APA
Chicago
ICMJE
MLA
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Sauters, T. J. C., Roth, C., Murray, D., Sun, S., Floyd Averette, A., Onyishi, C. U., … Magwene, P. M. (2023). Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis. PLoS Pathog, 19(11), e1011763. https://doi.org/10.1371/journal.ppat.1011763
Sauters, Thomas J. C., Cullen Roth, Debra Murray, Sheng Sun, Anna Floyd Averette, Chinaemerem U. Onyishi, Robin C. May, Joseph Heitman, and Paul M. Magwene. “Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis.PLoS Pathog 19, no. 11 (November 2023): e1011763. https://doi.org/10.1371/journal.ppat.1011763.
Sauters TJC, Roth C, Murray D, Sun S, Floyd Averette A, Onyishi CU, et al. Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis. PLoS Pathog. 2023 Nov;19(11):e1011763.
Sauters, Thomas J. C., et al. “Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis.PLoS Pathog, vol. 19, no. 11, Nov. 2023, p. e1011763. Pubmed, doi:10.1371/journal.ppat.1011763.
Sauters TJC, Roth C, Murray D, Sun S, Floyd Averette A, Onyishi CU, May RC, Heitman J, Magwene PM. Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis. PLoS Pathog. 2023 Nov;19(11):e1011763.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

November 2023

Volume

19

Issue

11

Start / End Page

e1011763

Location

United States

Related Subject Headings

  • Virology
  • Predatory Behavior
  • Mice
  • Metagenomics
  • Humans
  • Cryptococcus neoformans
  • Cryptococcosis
  • Animals
  • Amoeba
  • 3207 Medical microbiology