Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis

Abstract

Cryptococcus neoformans, an encapsulated basidiomycete fungus of medical importance, is capable of crossing the blood-brain barrier and causing meningitis in both immunocompetent and immunocompromised individuals. To gain insight into the adaptation of the fungus to the host central nervous system (CNS), serial analysis of gene expression (SAGE) was used to characterize the gene expression profile of C. neoformans cells recovered from the CNS of infected rabbits. A SAGE library was constructed, and 49,048 tags were sequenced; 16,207 of these tags were found to represent unique sequences or tag families. Of the 304 most-abundant tags, 164 were assigned to a putative gene for subsequent functional grouping. The results (as determined according to the number of tags that identified genes encoding proteins required for these functions) indicated that the C. neoformans cells were actively engaged in protein synthesis, protein degradation, stress response, smallmolecule transport, and signaling. In addition, a high level of energy requirement of the fungal cells was suggested by a large number of tags that matched putative genes for energy production. Taken together, these findings provide the first insight into the transcriptional adaptation of C. neoformans to the host environment and identify the set of fungal genes most highly expressed during cerebrospinal fluid infection.

Characterization and Regulation of the Trehalose Synthesis Pathway and Its Importance in the Pathogenicity of Cryptococcus neoformans

“…Trehalose is composed of two glucose molecules linked at their 1-carbons and is rapidly produced under various cellular stresses. Two recent studies have identified both trehalose and the expression of genes in its pathway at the sites of cryptococcal infections, and these results reinforce the potential importance of the trehalose pathway in C. neoformans survival within the host (28,50).…”

“…First, in a global transcriptional gene analysis, CSF was removed from rabbits infected with cryptococcal meningitis. With the use of serial analysis of gene expression for identification and quantitation of transcripts from yeast cells within the CSF, one of the genes most highly expressed was TPS1 (50). Second, the potential importance of the trehalose pathway for the yeast within the central nervous system was further supported when tissues surrounding cryptococcomas from infected rat brains and lungs were analyzed by NMR studies (28,29).…”

The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation

“…For strains that did not cause mortality of 50% or more within the 45-day timeframe of the experiment, we arbitrarily assigned an ST 50 of 55 days. system infection (16,17). Taken together, we propose that mitochondrial function is critical for the virulence of this lineage.…”

Proteomic analysis of dimorphic transition in the phytopathogenic fungus Ustilago maydis

“…Within the small subset of four coregulated protein spots, we identified a homologue of CipC (UM03284), a small conserved fungal protein with unknown biological function. CipC was first identified as a concanamycin induced protein in Aspergillus nidulans and homologues have since been found to be induced under many different conditions: it is up-regulated during ectomycorrhizal symbiosis in Paxillus species, in experimental cryptococcal meningitis and by nitrogen starvation in Gibberella fujikuroi [26][27][28][29]. CipC is also significantly up-regulated under conditions of nitrogen starvation in U. maydis (M. Bölker, unpublished results).…”