Identification and transcriptional regulation of l-cysteine transporter Mup1 in Cryptococcus neoformans

Abstract:

[Objective] To identify the l-cysteine transporter of Cryptococcus neoformans and study the effect of the transporter on the fungal pathogenicity. [Methods] We constructed the candidate gene-deleted strains, and examined the growth of the mutants with l-cysteine as the sole sulfur source. We then tested the effect of the l-cysteine transporter Mup1 on the expression of virulence factors and the growth of C. neoformans under different stress conditions. Further, we used the Galleria mellonella infection model and the mouse infection model to explore the effect of MUP1 on the pathogenicity of C. neoformans. RNA-Seq and yeast one-hybrid assay were employed to investigate the regulatory relationship between the master transcription factor Cys3 and Mup1. [Results] Mup1 could transport l-cysteine, l-cystine, dl-cystathionine, and l-homocysteine. The deletion of gene MUP1 did not affect the expression of virulence factors or the cellular response to stress. Mup1 had no significant effect on the pathogenicity of C. neoformans in G. mellonella and mice. Cys3 might indirectly regulate the transcription of MUP1. [Conclusion] Mup1 is the transporter of l-cysteine, l-cystine, dl-cystathionine, and l-homocysteine in C. neoformans. It does not affect the pathogenicity of C. neoformans and may be indirectly regulated by Cys3.

Key words:Cryptococcus neoformans;transporter;l-cysteine;pathogenicity;regulatory relationship