TupA, the Penicillium marneffei Tup1p homologue, represses both yeast and spore development

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 25degreesC as filamentous multinucleate hyphae switching at 37degreesC 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 25degreesC, 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.