ArticlePLoS biology2013
A temperature-responsive network links cell shape and virulence traits in a primary fungal pathogen.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed.
- Polyphenism Through RNA Chemical Modifications.Molecular ecology · 2026Review
- The Rpd3 histone deacetylase is a critical regulator of temperature-mediated morphogenesis and virulence in the human fungal pathogen Histoplasma.PLoS biology · 2026Article
- The global regulator LaeA controls expression of genes involved in diverse primary and secondary metabolites biosynthesis and their secretion in fungi.Frontiers in microbiology · 2026Review
- Rapid gain and loss of a chromosome drives key morphology and virulence phenotypes in the fungal pathogen Histoplasma.PLoS biology · 2026Article
- Article
- "Select and Resequence" Methods Enable a Genome-Wide Association Study of the Dimorphic Human Fungal Pathogen Coccidioides posadasii.Genome biology and evolution · 2025Article
- Signaling Pathways Regulating Dimorphism in Medically Relevant Fungal Species.Pathogens (Basel, Switzerland) · 2025Review
- Transcriptomic atlas throughout Coccidioides development reveals key phase-enriched transcripts of this important fungal pathogen.PLoS biology · 2025Article
- Article
- 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
- Genotypic diversity, virulence, and molecular genetic tools inMicrobiology and molecular biology reviews : MMBR · 2024Review
- Article
- The Host Response to Coccidioidomycosis.Journal of fungi (Basel, Switzerland) · 2024Review
- Histoplasmosis in Solid Organ Transplantation.Journal of fungi (Basel, Switzerland) · 2024Review
- Phase separation in fungi.Nature microbiology · 2023Review
- A novel biosensor for ultrasensitive detection of fungal genes.Biosensors & bioelectronics · 2023Article
- Fungal resilience and host-pathogen interactions: Future perspectives and opportunities.Parasite immunology · 2023Review
- Pathogenicity & virulence ofVirulence · 2022Review
- The Role of the Glutathione System in Stress Adaptation, Morphogenesis and Virulence of Pathogenic Fungi.International journal of molecular sciences · 2022Review
22 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
Abstract
Survival at host temperature is a critical trait for pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are soil fungi that undergo dramatic changes in cell shape and virulence gene expression in response to host temperature. How these organisms link changes in temperature to both morphologic development and expression of virulence traits is unknown. Here we elucidate a temperature-responsive transcriptional network in H. capsulatum, which switches from a filamentous form in the environment to a pathogenic yeast form at body temperature. The circuit is driven by three highly conserved factors, Ryp1, Ryp2, and Ryp3, that are required for yeast-phase growth at 37°C. Ryp factors belong to distinct families of proteins that control developmental transitions in fungi: Ryp1 is a member of the WOPR family of transcription factors, and Ryp2 and Ryp3 are both members of the Velvet family of proteins whose molecular function is unknown. Here we provide the first evidence that these WOPR and Velvet proteins interact, and that Velvet proteins associate with DNA to drive gene expression. Using genome-wide chromatin immunoprecipitation studies, we determine that Ryp1, Ryp2, and Ryp3 associate with a large common set of genomic loci that includes known virulence genes, indicating that the Ryp factors directly control genes required for pathogenicity in addition to their role in regulating cell morphology. We further dissect the Ryp regulatory circuit by determining that a fourth transcription factor, which we name Ryp4, is required for yeast-phase growth and gene expression, associates with DNA, and displays interdependent regulation with Ryp1, Ryp2, and Ryp3. Finally, we define cis-acting motifs that recruit the Ryp factors to their interwoven network of temperature-responsive target genes. Taken together, our results reveal a positive feedback circuit that directs a broad transcriptional switch between environmental and pathogenic states in response to temperature.
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