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Abstract Detail



Karling Lecture - Anita Sil

Sil, Anita [1].

Regulation of cell shape and virulence in response to temperature in the fungal pathogen Histoplasma .

We share this planet with over six million fungal species spanning hundreds of millions of years of evolution, and yet we have molecular knowledge about only a small subset of organisms. It is estimated that there are 600 fungal species associated with humans as either commensals or pathogens, but very little is understood about how these organisms interact with and influence their mammalian hosts. Our work illuminates the biology of a small, evolutionarily related group of fungi (thermally dimorphic fungal pathogens) that cause disease even in otherwise healthy humans. These fungi display beautiful and intricate biology that underlies complex behaviors such as elaborate responses to host temperature, evasion of human defenses, and colonization of host immune cells. One long-term goal of our research is to determine how environmental signals such as temperature regulate morphology and virulence in the fungal pathogens Histoplasma and Coccidioides. Histoplasma grows in a multicellular filamentous form in the soil; once inhaled into a mammalian host, these cells switch their growth program to a unicellular parasitic yeast form that subverts the innate immune system to cause disease. Temperature is a key signal that regulates this morphogenetic switch, and we are intrigued by how this pathogenic microbe senses and responds to temperature. We identified the first transcriptional regulators required for growth in the yeast form in response to host temperature. These factors, named Ryp proteins, are orthologous to key developmental regulators in other fungi, and represent critical elements of the temperature-dependent regulatory circuit in Histoplasma. In recent work, we have discovered a cell surface protein (Msb2), a MAP kinase (Hog2), and a transcription factor (Stu1) that are required for filamentation at room temperature. Transcriptional profiling revealed that Msb2 is required for the expression of a small cohort of genes that are regulated by temperature and required for filamentation. Interestingly, our data indicate that the Ryp pathway and the Msb2 pathway antagonize each other, and that temperature determines which pathway dominates. Similarly, we are exploring regulatory circuits that control temperature response and virulence in Coccidioides. Ultimately we hope to elucidate an integrated pathway of thermosensory and thermoresponsive proteins required for Histoplasma and Coccidioides to thrive either in the soil or in the mammalian host.


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1 - UCSF Integrative Microbiology

Keywords:
none specified

Presentation Type: Special Presentations
Session: S12, Karling Lecture - Anita Sil
Location: Virtual/Virtual
Date: Thursday, July 22nd, 2021
Time: 1:30 PM
Number: S12001
Abstract ID:1145
Candidate for Awards:None


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