Cross-Kingdom Control: Yeast Prion Protein Modulates Host Physiology in Drosophila
- 1Cornell University
Abstract
Prions, once mainly studied for their pathogenic roles, are now gaining recognition as adaptive elements in microbial physiology. Over one-third of wild yeast isolates harbor prion proteins, yet their impact on host-microbe interactions remains poorly characterized. Given the ecological dominance of yeasts in the Drosophila mycobiome, we leveraged the Drosophila melanogaster-Saccharomyces cerevisiae system to investigate how the mycobiome-derived prion, [MRPL10+], modulates host physiology. We show that flies exposed to [MRPL10+] yeast exhibit significantly enhanced cold tolerance and increased locomotor activity. This effect persists with heat-killed yeast and diluted culture, suggesting a stable, potent bioactive factor. Using the genetically diverse Drosophila Global Diversity Lines (GDL), we identified natural variation in responsiveness to [MRPL10+] yeast. Genome-wide association and functional RNAi screening revealed a gut-brain signaling axis involving genes critical for digestion, intercellular communication, transcription regulation, and neural transmission. Notably, serotonin and octopamine pathways were essential for [MRPL10+]-induced changes in cold tolerance and locomotion, implicating neuromodulatory circuits in prion-mediated microbial signaling. Our findings establish a mechanistic link between a fungal prion and host metabolic and neural adaptation. This work provides the first genetic dissection of a prion-mediated host-microbe interaction, laying the groundwork for investigating beneficial prions in complex microbial communities and highlighting a new dimension of the mycobiomes influence on animal physiology.
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BibTeX
@misc{clark2026crosskingdom,
title = {{Cross-Kingdom Control: Yeast Prion Protein Modulates Host Physiology in Drosophila}},
author = {A. G. Clark and J. Y. Jiang and M. D. Chitale and E. Cosgrove and A. Van Elgort and A. M. Jain and J. C. Kelso and X. Cui and N. Yapici and C.-c. Lin},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.26.747210},
url = {https://www.biorxiv.org/content/10.64898/2026.08.26.747210v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cross-Kingdom Control: Yeast Prion Protein Modulates Host Physiology in Drosophila
AU - A. G. Clark
AU - J. Y. Jiang
AU - M. D. Chitale
AU - E. Cosgrove
AU - A. Van Elgort
AU - A. M. Jain
AU - J. C. Kelso
AU - X. Cui
AU - N. Yapici
AU - C.-c. Lin
PY - 2026
DA - 2026/08/26
PB - bioRxiv
DO - 10.64898/2026.08.26.747210
UR - https://www.biorxiv.org/content/10.64898/2026.08.26.747210v1
AB - Prions, once mainly studied for their pathogenic roles, are now gaining recognition as adaptive elements in microbial physiology. Over one-third of wild yeast isolates harbor prion proteins, yet their impact on host-microbe interactions remains poorly characterized. Given the ecological dominance of yeasts in the Drosophila mycobiome, we leveraged the Drosophila melanogaster-Saccharomyces cerevisiae system to investigate how the mycobiome-derived prion, [MRPL10+], modulates host physiology. We show that flies exposed to [MRPL10+] yeast exhibit significantly enhanced cold tolerance and increased locomotor activity. This effect persists with heat-killed yeast and diluted culture, suggesting a stable, potent bioactive factor. Using the genetically diverse Drosophila Global Diversity Lines (GDL), we identified natural variation in responsiveness to [MRPL10+] yeast. Genome-wide association and functional RNAi screening revealed a gut-brain signaling axis involving genes critical for digestion, intercellular communication, transcription regulation, and neural transmission. Notably, serotonin and octopamine pathways were essential for [MRPL10+]-induced changes in cold tolerance and locomotion, implicating neuromodulatory circuits in prion-mediated microbial signaling. Our findings establish a mechanistic link between a fungal prion and host metabolic and neural adaptation. This work provides the first genetic dissection of a prion-mediated host-microbe interaction, laying the groundwork for investigating beneficial prions in complex microbial communities and highlighting a new dimension of the mycobiomes influence on animal physiology.
ER -