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Transcriptomic atlas throughout Coccidioides development reveals key phase-enriched transcripts of this important
Christina M Homer1, Mark Voorhies2, Keith Walcott2
1Division of Infectious Diseases, University of California San Francisco, San Francisco, California, United States of America.
Plos Biology
|April 15, 2025
Summary
This study reveals key gene expression changes during Coccidioides fungal development, identifying RYP1-dependent transcripts crucial for spherulation and virulence. These findings advance our understanding of this significant pathogen.
Area of Science:
- Medical Mycology
- Fungal Pathogenesis
- Transcriptomics
Background:
- Coccidioides spp. are significant fungal pathogens causing coccidioidomycosis.
- Their unique dimorphic transition, spherulation, is essential for virulence but poorly understood.
- RYP1 is a known regulator of spherulation and virulence.
Purpose of the Study:
- To perform high-density transcriptomic analysis of Coccidioides development.
- To identify morphology-dependent transcripts and RYP1-regulated genes.
- To uncover molecular determinants of spherulation and virulence.
Main Methods:
- High-density transcriptomic analysis (RNA-Seq).
- Chromatin immunoprecipitation sequencing (ChIP-Seq) for Ryp1 regulon identification.
- Analysis of approximately 9,000 predicted transcripts.
Main Results:
- Identified 273 transcripts with spherule-associated expression, 82 of which are RYP1-dependent.
- Discovered distinct Ryp1 regulons in hyphae and spherules.
- Found 20 endospore-enriched transcripts and 14 spherule-enriched putative secreted effectors, including six proteases.
Conclusions:
- This study provides a comprehensive transcriptomic resource for Coccidioides development.
- RYP1 plays a central role in regulating spherule-specific gene expression and virulence.
- The identified virulence factors offer potential targets for therapeutic intervention.
