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Host environmental conditions induce small fungal cell size and alter population heterogeneity in Cryptococcus neoformans

By Xin Zhou, Hanna Zafar, Poppy Sephton-Clark, Sally H Mohamed, Ambre Chapuis, Maria Makarova, Donna M. MacCallum, Rebecca A. Drummond, Ivy M Dambuza, Elizabeth R. Ballou

Posted 06 Jan 2020
bioRxiv DOI: 10.1101/2020.01.03.894709

Fungal morphology significantly impacts the host response. Filamentation and tissue penetration by Candida and Aspergillus species are essential for virulence, while growth as a yeast allows the thermal dimorphic fungi Coccidiodes, Histoplasma , and Talaromyces to reside inside phagocytes and disseminate. The basidiomycete Cryptococcus neoformans exhibits an unusual yeast-to-titan transition thought to enhance pathogenicity by increasing fungal survival in the host lung and dissemination to the central nervous system. In a common laboratory strain (H99), in vitro and in vivo titan induction yields a heterogenous population including >10 μm titan cells, 5-7 μm yeast cells and 2-4 μm titanides. Previous reports have shown that titan cells are associated with enhanced virulence and the generation of aneuploid cells that facilitate stress adaptation and drug resistance, while small (>10 μm) cells are associated with increased dissemination. However, the relationship between titan cells, small cells, and titanides remains unclear. Here, we characterize titanides and small cells in H99 and three clinical isolates and show that titanides share the lipid membrane order of their titan mothers and the G0 quiescent-like DNA staining of mating spores. In addition, we show that both titanizing and non-titanizing isolates exhibit altered capsule structure and PAMP exposure over time during in vitro culture, and generate aneuploidy in vivo. ### Competing Interest Statement The authors have declared no competing interest.

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