Role of Glucose in the Expression of Cryptococcus neoformans Antiphagocytic Protein 1, App1

Abstract

ABSTRACTThe cryptococcus-specific protein antiphagocytic protein 1 (App1) regulatesCryptococcus neoformansvirulence by controlling macrophage-driven fungal phagocytosis. This is accomplished through complement receptors (CR), specifically CR3. When inhaled,C. neoformanscan cause a life-threatening meningoencephalitis in immunocompromised patients. Because glucose starvation can significantly change the gene expression and virulence ofC. neoformansand because App1 is critical for phagocytosis in the lung—a low-glucose environment—we investigated the role of glucose in App1 expression. We found that App1 was upregulated dramatically under low-glucose conditions, and it was upregulated whenC. neoformanscells were incubated in bronchoalveolar lavage (BAL) fluid, serum, and cerebrospinal fluid, which are low-glucose environments. Characterization of App1's regulation based on mammalian lung physiology revealed that App1 is upregulated via both increases in transcription and increases in mRNA stability. Our data provide new insights regardingC. neoformansadaptations to low-glucose environments.