Elucidation of the function of beta-1,6-glucan and investigation of chitin deacetylase localization in Cryptococcus neoformans.

摘要

Cryptococcus neoformans is an opportunistic human fungal pathogen causing life-threatening meningoencephalitis. Current therapies for cryptococcal infection are insufficient, as they either fail to clear the organism or display significant host toxicity. The C. neoformans cell wall is an attractive target for antimicrobial therapies. The fungal cell wall is vital for maintaining cell integrity and most of its components are absent from mammalian host cells. The cell wall is a complex meshwork consisting primarily of polysaccharides and proteins. We reveal what is important for maintaining this essential organelle by studying the genes and enzymes responsible for cell wall biogenesis. We show that the polysaccharide beta-1,6-glucan is required for maintaining cell wall integrity and association of known cryptococcal virulence factors. We discovered an involvement of beta-1,6-glucan synthesis-related genes in the mating cycle of C. neoformans. Finally, we determined the cellular mechanisms controlling localization of an enzyme responsible for synthesis of the cell wall polymer chitosan and describe the requirement of its localization pattern for chitosan production. Overall, findings from these studies advance the understanding of C. neoformans cell wall biology and may lead to new avenues for therapeutic intervetion.