Cryptococcus neoformans of Unusual Morphology

Abstract

A case of primary cryptococcosis of the lungs was caused by an isolate of Cryptococcus neoformans that assumes a giant form in tissue but which has a normal appearance on artificial culture. Electron microscopy revealed gross enlargement of the capsule and plasma membranes in the tissue form.

An in vitro method for inducing titan cells reveals novel features of yeast-to-titan switching in the human fungal pathogen Cryptococcus gattii

“…C. neoformans titan cells have been clinically observed [11,12], studied in vivo [6,7] and recently induced in vitro [13][14][15]. The discovery of in vitro induction protocols is considered a major breakthrough, as efforts employed towards understanding the biology and mechanism underlying titanisation were impeded by the ethical and technical challenges associated with using animal models.…”

Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen

“…Recently, another dimorphic cellular transition, namely the formation of dramatically enlarged titan cells, has been identified and characterized in Cryptococcus species. While Cryptococcus typically grows as an encapsulated budding yeast (∼5 μm in diameter), titan cells are dramatically enlarged (>10 μm and up to more than 100 μm in diameter), polyploid (>2C and up to more than 128C in DNA content), and have cell wall and capsule characteristics distinct from those of standard yeast cells ( 39 – 44 ). The production of titan cells can be induced both in vitro and in vivo, and meiotic machinery has been implicated in regulating the ploidy transitions during this process ( 45 ).…”

An Immunogenic and Slow-Growing Cryptococcal Strain Induces a Chronic Granulomatous Infection in Murine Lungs

“…We next explored specific phenotypes of the mar1 Δ mutant strain that may drive the observed granulomatous response. In both human and murine infections, a subset of cryptococcal cells form enlarged Titan cells, an important virulence factor that suppresses fungal phagocytosis by host macrophages ( 30 , 32 ). Using an established in vitro titanization assay ( 33 ), we observed that the mar1 Δ mutant strain was unable to form Titan cells ( Fig.…”

“…We also characterized multiple mar1 Δ mutant strain phenotypes that may contribute to the granulomatous response and fungal persistence in this model. Titan cell formation is a well-characterized, Cryptococcus -specific persistence mechanism that suppresses fungal phagocytosis by host macrophages ( 30 , 32 ). Results from an established in vitro titanization assay ( 33 ), as well as our histopathological observations, demonstrated that the mar1 Δ mutant strain was impaired in the production of Titan cells.…”

“…Furthermore, recent work has proposed that C. neoformans undergoes a unique cell cycle in vivo , the “stress cell cycle,” that regulates the employment of various virulence factors ( 52 ). Titan cells are enlarged and polyploid cells that form in both human and mouse lungs during infection ( 30 , 32 ). This polyploidization and concomitant cell body enlargement is negatively regulated by the transcription factor Usv101, which acts downstream of the cell cycle regulator Swi6 ( 33 , 34 ).…”