A Wor1-Like Transcription Factor Is Essential for Virulence of Cryptococcus neoformans

Wor1 样转录因子对新型隐球菌的毒力至关重要

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作者:Hugo Costa Paes, Lorena da Silveira Derengowski, Luisa Defranco Ferreira Peconick, Patrícia Albuquerque, Georgios Joannis Pappas Jr, André Moraes Nicola, Fabiana Brandão Alves Silva, Marcelo Afonso Vallim, J Andrew Alspaugh, Maria Sueli Soares Felipe, Larissa Fernandes

Abstract

Gti1/Pac2 transcription factors occur exclusively in fungi and their roles vary according to species, including regulating morphological transition and virulence, mating and secondary metabolism. Many of these functions are important for fungal pathogenesis. We therefore hypothesized that one of the two proteins of this family in Cryptococcus neoformans, a major pathogen of humans, would also control virulence-associated cellular processes. Elimination of this protein in C. neoformans results in reduced polysaccharide capsule expression and defective cytokinesis and growth at 37°C. The mutant loses virulence in a mouse model of cryptococcal infection and retains only partial virulence in the Galleria mellonella alternative model at 30°C. We performed RNA-Seq experiments on the mutant and found abolished transcription of genes that, in combination, are known to account for all the observed phenotypes. The protein has been named Required for cytokinesis and virulence 1 (Rcv1).

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