ArticlePLoS pathogens2022
The WOPR family protein Ryp1 is a key regulator of gene expression, development, and virulence in the thermally dimorphic fungal pathogen Coccidioides posadasii.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 25 citations in OpenAlex.
- Transcriptomic characterization of Coccidioides morphological states using RiboMarker-enhanced RNA sequencing.G3 (Bethesda, Md.) · 2026Article
- Macrophage phagocytosis ofmBio · 2026Article
- Hybrid histidine kinases and antifungal warfare in thermal dimorphic fungi.Antimicrobial agents and chemotherapy · 2026Review
- Current perspectives of host-pathogen dynamics in coccidioidomycosis.Current opinion in microbiology · 2026Review
- Establishment of an RAA-CRISPR/Cas12a assay based onMicrobiology spectrum · 2025Article
- "Select and Resequence" Methods Enable a Genome-Wide Association Study of the Dimorphic Human Fungal Pathogen Coccidioides posadasii.Genome biology and evolution · 2025Article
- Transcriptomic atlas throughout Coccidioides development reveals key phase-enriched transcripts of this important fungal pathogen.PLoS biology · 2025Article
- OptimizingmSphere · 2025Article
- Transcriptomic atlas of the morphologic development of the fungal pathogenbioRxiv : the preprint server for biology · 2024Article
- Inferring the composition of a mixed culture of natural microbial isolates by deep sequencing.bioRxiv : the preprint server for biology · 2024Article
- Article
- The Host Response to Coccidioidomycosis.Journal of fungi (Basel, Switzerland) · 2024Review
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- Role of theJournal of fungi (Basel, Switzerland) · 2024Article
- Fungal Vaccine Development: State of the Art and Perspectives Using Immunoinformatics.Journal of fungi (Basel, Switzerland) · 2023Review
- Genome Organization and Copy-Number Variation Reveal Clues to Virulence Evolution inJournal of fungi (Basel, Switzerland) · 2022Article
- Coccidioides Species: A Review of Basic Research: 2022.Journal of fungi (Basel, Switzerland) · 2022Review
- Vaccines to Prevent Coccidioidomycosis: A Gene-Deletion Mutant of Coccidioides Posadasii as a Viable Candidate for Human Trials.Journal of fungi (Basel, Switzerland) · 2022Review
- Decoding Transcription Regulatory Mechanisms Associated withmSystems · 2022Article
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7 authors at 2 institutions in 1 country.
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Abstract
Coccidioides spp. are mammalian fungal pathogens endemic to the Southwestern US and other desert regions of Mexico, Central and South America, with the bulk of US infections occurring in California and Arizona. In the soil, Coccidioides grows in a hyphal form that differentiates into 3-5 micron asexual spores (arthroconidia). When arthroconidia are inhaled by mammals they undergo a unique developmental transition from polar hyphal growth to isotropic expansion with multiple rounds of nuclear division, prior to segmentation, forming large spherules filled with endospores. Very little is understood about the molecular basis of spherule formation. Here we characterize the role of the conserved transcription factor Ryp1 in Coccidioides development. We show that Coccidioides Δryp1 mutants have altered colony morphology under hypha-promoting conditions and are unable to form mature spherules under spherule-promoting conditions. We analyze the transcriptional profile of wild-type and Δryp1 mutant cells under hypha- and spherule-promoting conditions, thereby defining a set of hypha- or spherule-enriched transcripts ("morphology-regulated" genes) that are dependent on Ryp1 for their expression. Forty percent of morphology-regulated expression is Ryp1-dependent, indicating that Ryp1 plays a dual role in both hyphal and spherule development. Ryp1-dependent transcripts include key virulence factors such as SOWgp, which encodes the spherule outer wall glycoprotein. Concordant with its role in spherule development, we find that the Δryp1 mutant is completely avirulent in the mouse model of coccidioidomycosis, indicating that Ryp1-dependent pathways are essential for the ability of Coccidioides to cause disease. Vaccination of C57BL/6 mice with live Δryp1 spores does not provide any protection from lethal C. posadasii intranasal infection, consistent with our findings that the Δryp1 mutant fails to make mature spherules and likely does not express key antigens required for effective vaccination. Taken together, this work identifies the first transcription factor that drives mature spherulation and virulence in Coccidioides.
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