The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis

PLoS Pathogens
Ivy M DambuzaElizabeth R Ballou

Abstract

Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis and niche adaptation. For example, dimorphic fungi switch between yeast and hyphae in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from haploid yeast to large, highly polyploid cells termed Titan cells. Titan cells influence fungal interaction with host cells, including through increased drug resistance, altered cell size, and altered Pathogen Associated Molecular Pattern exposure. Despite the important role these cells play in pathogenesis, understanding the environmental stimuli that drive the morphological transition, and the molecular mechanisms underlying their unique biology, has been hampered by the lack of a reproducible in vitro induction system. Here we demonstrate reproducible in vitro Titan cell induction in response to environmental stimuli consistent with the host lung. In vitro Titan cells exhibit all the properties of in vivo generated Titan cells, the current gold standard, including altered capsule, cell wall, size, high mother cell ploidy, and aneuploid progeny. We identify the bacterial peptidoglycan ...Continue Reading

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Citations

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Methods Mentioned

BETA
FCS
flow cytometry
Lavage
size exclusion chromatography
Nucleotide Exchange
FACS
dissection
PCR

Software Mentioned

Graph Pad Prism
ARRIVE
Graphpad Prism

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