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Treffer: Unisexual reproduction in the global human fungal pathogen Cryptococcus neoformans .

Title:
Unisexual reproduction in the global human fungal pathogen Cryptococcus neoformans .
Authors:
Sun S; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710., Bian Z; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710., Xu Z; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710., Choi Y; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710., Heitman J; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
Source:
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2025 Oct 21; Vol. 122 (42), pp. e2521779122. Date of Electronic Publication: 2025 Oct 14.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Imprint Name(s):
Original Publication: Washington, DC : National Academy of Sciences
MeSH Terms:
Cryptococcus neoformans*/genetics , Cryptococcus neoformans*/physiology , Cryptococcus neoformans*/pathogenicity , Reproduction, Asexual*/genetics, Humans ; Genes, Mating Type, Fungal ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Guanine Nucleotide Exchange Factors/genetics ; Guanine Nucleotide Exchange Factors/metabolism ; Reproduction ; Genetic Variation ; Cryptococcosis/microbiology ; Meiosis ; Recombination, Genetic ; Mutation
Comments:
Update of: bioRxiv. 2025 Sep 02:2025.06.02.657540. doi: 10.1101/2025.06.02.657540.. (PMID: 40502051)
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Grant Information:
AI039115 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); AI133654 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R01 AI172451 United States AI NIAID NIH HHS; AI050113 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); AI172451 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R01 AI133654 United States AI NIAID NIH HHS; R01 AI050113 United States AI NIAID NIH HHS; AI170543 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R01 AI170543 United States AI NIAID NIH HHS; R01 AI039115 United States AI NIAID NIH HHS
Contributed Indexing:
Keywords: G protein; Ric8; fungi; guanine nucleotide exchange factor (GEF); sexual development
Substance Nomenclature:
0 (Fungal Proteins)
0 (Guanine Nucleotide Exchange Factors)
Entry Date(s):
Date Created: 20251014 Date Completed: 20251014 Latest Revision: 20251119
Update Code:
20251119
PubMed Central ID:
PMC12557769
DOI:
10.1073/pnas.2521779122
PMID:
41086205
Database:
MEDLINE

Weitere Informationen

The human fungal pathogen Cryptococcus species complex (encompassing Cryptococcus neoformans , Cryptococcus deneoformans , and the Cryptococcus gattii species complexes) exhibits diversity in sexual reproduction, including α- a mating, pseudosexual reproduction, as well as unisexual reproduction initiated from a single isolate or between isolates of the same mating type. A central conundrum is that while most Cryptococcus natural populations exhibit significant α mating-type bias, genetic and genomic analyses show recombination occurs in nature. The discovery of unisexual reproduction in C. deneoformans provided insight; however, thus far, unisexual reproduction has never been directly observed in the predominant global pathogenic species C. neoformans . Here, we provide evidence that mutating the RIC8 gene, which encodes a conserved guanine nucleotide exchange factor (GEF) involved in both chaperoning and activating Gα proteins, enables unisexual reproduction in C. neoformans . Additionally, we show that genetic variation in the natural population promotes unisexual reproduction, and unisexual reproduction in C. neoformans involves canonical meiotic recombination. Finally, we found that deletion of both GPA2 and GPA3 in the MAT α background leads to self-filamentation without sporulation, suggesting that differential modulation of the Gα proteins, likely involving Ric8, could underlie the switch between different modes of sexual reproduction in Cryptococcus . Our study further highlights that the highly conserved Ric8 GEF can act as an important regulator of cellular development in response to environmental stimuli and could modulate sexual reproduction in nature. We hypothesize that unisexual reproduction occurs much more frequently in nature than currently appreciated, and possibly in other fungi and microbial eukaryotes as well.

Competing interests statement:We note that one of the two external reviewers (A.P.M.) coauthored a conference paper with a total of 34 coauthors (Case et al., G3 2022), including one of the authors here (J.H.).