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Published on: September 17, 2016
TupA, the Penicillium marneffei Tup1p homologue, represses both yeast and spore development
Richard B Todd1, Jennifer R Greenhalgh, Michael J Hynes
1Department of Genetics, The University of Melbourne, 3010, Australia.
Abstract:
Fungal pathogenesis is frequently associated with dimorphism - morphological changes between yeast and filamentous forms. Penicillium marneffei, an opportunistic human pathogen, exhibits temperature-dependent dimorphism, with growth at 25 degrees C as filamentous multinucleate hyphae switching at 37 degrees C to uninucleate yeast cells associated with intracellular pathogenesis. The filamentous hyphae also undergo asexual development generating uninucleate spores, the infectious propagules. Both processes require a switch to coupled nuclear and cell division. Homologous regulators, including Tup1p/GROUCHO-related WD40 repeat transcription factors, control dimorphism in Candida albicans and asexual development in Aspergillus nidulans. Unlike these fungi, P. marneffei has both developmental programmes allowing examination of common and programme-specific controls. We show that deletion of tupA, the P. marneffei TUP1 homologue, confers reduced filamentation and inappropriate yeast morphogenesis at 25 degrees C, in stark contrast to constitutive filamentation observed when C. albicans TUP1 is deleted. Deletion of tupA also confers premature brlA-dependent asexual development, unlike reduced asexual development in the corresponding A. nidulans rcoA deletion mutant. Furthermore, the A. nidulans rcoA deletion mutant is self-sterile, and we show that tupA from P. marneffei, which lacks an apparent sexual cycle, complements both the asexual and sexual development phenotypes. Therefore, TupA coordinates cell fate by promoting filamentation and repressing both spore and yeast morphogenetic programmes.
Insights
Penicillium marneffei
Area of Science:
- Mycology
- Molecular Biology
- Fungal Pathogenesis
Background:
- Fungal dimorphism, the transition between yeast and filamentous forms, is crucial for pathogenesis.
- Penicillium marneffei, an opportunistic pathogen, displays temperature-dependent dimorphism and asexual development.
- Understanding the regulation of these developmental programs is key to controlling fungal infections.
Purpose of the Study:
- To investigate the role of the TUP1 homologue, TupA, in regulating dimorphism and asexual development in P. marneffei.
- To compare the function of TupA in P. marneffei with its homologues in other fungi like Candida albicans and Aspergillus nidulans.
- To elucidate how TupA coordinates distinct developmental pathways in P. marneffei.
Main Methods:
- Gene deletion of the P. marneffei TUP1 homologue (tupA).
- Phenotypic analysis of the tupA deletion mutant at different temperatures (25°C and 37°C).
- Complementation studies using P. marneffei tupA in Aspergillus nidulans mutants.
Main Results:
- Deletion of tupA in P. marneffei resulted in reduced filamentation and aberrant yeast growth at 25°C.
- tupA deletion led to premature, brlA-dependent asexual development.
- P. marneffei tupA complemented both asexual and sexual development defects in an A. nidulans mutant.
Conclusions:
- TupA acts as a master regulator, promoting filamentous growth while repressing yeast and spore formation in P. marneffei.
- TupA coordinates cell fate decisions, influencing both dimorphism and asexual development.
- The findings highlight conserved and unique roles of Tup1-like proteins in fungal development.
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