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IP 7 -SPX Domain Interaction Controls Fungal Virulence by Stabilizing Phosphate Signaling Machinery

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Desmarini Desmarini, Lev Sophie, Furkert David, Crossett Ben, Saiardi Adolfo, Kaufman-Francis Keren, Li Cecilia, Sorrell Tania C., Wilkinson-White Lorna, Matthews Jacqueline, Fiedler Dorothea, Djordjevic Julianne Teresa,
Project Discovery and mechanistic dissection of novel signaling pathways controlling phosphate homeostasis in eukaryotes
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Original article (peer-reviewed)

Journal mBio
Volume (Issue) 11(5)
Page(s) 1 - 10
Title of proceedings mBio
DOI 10.1128/mbio.01920-20

Open Access

URL http://doi.org/10.1128/mBio.01920-20
Type of Open Access Publisher (Gold Open Access)

Abstract

Invasive fungal diseases pose a serious threat to human health globally with >1.5 million deaths occurring annually, 180,000 of which are attributable to the AIDS-related pathogen, Cryptococcus neoformans . Here, we demonstrate that interaction of the inositol pyrophosphate, IP 7 , with the CDK inhibitor protein, Pho81, is instrumental in promoting fungal virulence. IP 7 -Pho81 interaction stabilizes Pho81 association with other CDK complex components to promote PHO pathway activation and phosphate acquisition. Our data demonstrating that blocking IP 7 -Pho81 interaction or preventing Pho81 production leads to a dramatic loss in fungal virulence, coupled with Pho81 having no homologue in humans, highlights Pho81 function as a potential target for the development of urgently needed antifungal drugs.
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