Inositol Metabolism Regulates Capsule Structure and Virulence in the Human Pathogen Cryptococcus neoformans
Yina Wang, Maggie Wear, Gurkirat Kohli, Raghav Vij, Charles Giamberardino, Arpun Shah, Dena L. Toffaletti, Chen-Hsin A. Yu, John R. Perfect, Arturo Casadevall, Chaoyang Xue
Abstract
-inositol oxygenase, a key enzyme in the inositol catabolic pathway. Expression of these genes is highly induced by inositol, and they are highly expressed in the cerebrospinal fluid of patients with meningoencephalitis. Our mutagenesis analysis indeed demonstrates that inositol catabolism is required for C. neoformans virulence by altering the growth and structure of polysaccharide capsule, a major virulence factor. Considering the abundance of free inositol and inositol-related metabolites in the brain, our study reveals an important mechanism of host inositol-mediated fungal pathogenesis for this neurotropic fungal pathogen.