Systematic Profiling of Host-derived Cues for the Regulation of Pathogenicity-associated Transcription factors in Human Fungal Pathogen Cryptococcus neoformans

Cryptococcus neoformans is a causative agent of global fungal meningoencephalitis, which results in more than 180,000 deaths annually. To analyze this pathogen, in vivo transcription profiling was performed to monitor 180 transcription factors (TFs) during the infection process. Here, we focused on 12 TFs that strongly induced in HMC. To classify which host factor causes the induction of genes during infection, HMC signals were dissected into temperature, carbon, and nitrogen starvation. Notably, we found that three distinct cues made a significant contribution to the regulation of their expression. The expression of six genes was markedly induced by temperature upshift. Also, the expression of six genes was highly induced by glucose starvation, and nine genes were highly induced by nitrogen starvation. Deletion of MLN1 caused growth defects supplemented with maltose or ammonium sulfate in a nutrient starvation medium, and transcriptome data of mln1Δ at the carbon starvation implied that MLN1 related to the L-leucine degradation pathway. In conclusion, we systematically dissected host-signaling cues that affect in vivo expression of pathogenicity-related TFs, providing further insight into complex signaling pathways modulating the host-pathogen interactions of C. neoformans.