Projects per year
Abstract
Cryptococcosis is a potentially lethal fungal infection of humans caused by organisms within the Cryptococcus neoformans/gattii species complex. Whilst C. neoformans is a relatively common pathogen of immunocompromised individuals, C. gattii is capable of acting as a primary pathogen of immunocompetent individuals. Within the host, both species undergo morphogenesis to form titan cells: exceptionally large cells that are critical for disease establishment. To date, the induction, defining attributes, and underlying mechanism of titanisation have been mainly characterized in C. neoformans. Here, we report the serendipitous discovery of a simple and robust protocol for in vitro induction of titan cells in C. gattii. Using this in vitro approach, we reveal a remarkably high capacity for titanisation within C. gattii, especially in strains associated with the Pacific Northwest Outbreak, and characterise strain-specific differences within the clade. In particular, this approach demonstrates for the first time that cell size changes, DNA amplification, and budding are not always synchronous during titanisation. Interestingly, however, exhibition of these cell cycle phenotypes was correlated with genes associated with cell cycle progression including CDC11, CLN1, BUB2, and MCM6. Finally, our findings reveal exogenous p-Aminobenzoic acid to be a key inducer of titanisation in this organism. Consequently, this approach offers significant opportunities for future exploration of the underlying mechanism of titanisation in this genus.
Original language | English |
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Article number | e1010321 |
Number of pages | 26 |
Journal | PLoS Pathogens |
Volume | 18 |
Issue number | 8 |
Early online date | 15 Aug 2022 |
DOIs | |
Publication status | E-pub ahead of print - 15 Aug 2022 |
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Immunology
- Molecular Biology
- Genetics
- Virology
Fingerprint
Dive into the research topics of 'An in vitro method for inducing titan cells reveals novel features of yeast-to-titan switching in the human fungal pathogen Cryptococcus gattii'. Together they form a unique fingerprint.Projects
- 2 Finished
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Sense and respond: Investigating molecular mechanisms regulating Cryptococcus neoformans Titan cell formation in response to bacterial triggers
Ballou, L.
1/10/18 → 20/05/21
Project: Research
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THE ROLE OF EXTRACELLULAR VESICLES IN REGULATING DIVISION OF LABOUR IN FUNGI
Dunn, W. & May, R.
Biotechnology & Biological Sciences Research Council
1/03/18 → 31/12/21
Project: Research Councils