title: Allergen1 regulates polysaccharide structure in Cryptococcus neoformans.
abstract: Cryptococcus neoformans is an important human, fungal pathogen that sheds polysaccharide (exo-PS) into host tissues. While shed exo-PS mediates numerous untoward effects (including promoting increased intracranial pressure), little is known about the regulation of this phenomenon. Since downregulation of the Allergen 1 (ALL1) gene is associated with high ICP, we investigated the relationship between ALL1 expression and exo-PS structure using a variety of biophysical techniques. The Δall1 mutants of two serotypes produced a shorter exo-PS with less branching and structural complexity than the parental strains. Consistent with lower branching, these exo-PSs manifested higher intrinsic viscosity than the parental strains. The Δall1 mutant strains manifested differences in epitope expression and significant resistance to phagocytosis. Exo-PS of Δall1 mutant exhibited anti-phagocytic properties. Comparative transcriptome analysis of mutant and parental strain under iron-deprived conditions indicated a role of ALL1 in iron homeostasis, characterized by differential regulation of genes that mediate iron reduction and transport. Together, our results demonstrate a role of ALL1 in regulating conformational aspects of PS structure and iron homeostasis. These findings provide a mechanism to explain how changes in ALL1 expression influence virulence of switch variants and suggest that structural changes and polymer length are epigenetically regulated.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Neena
authors.initials: N
authors.lastname: Jain
authors.forename: Radames J B
authors.initials: RJ
authors.lastname: Cordero
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.forename: Bettina C
authors.initials: BC
authors.lastname: Fries
mesh_terms: D000946:Antigens, Fungal / Q000235:genetics / Q000378:metabolism*; D003455:Cryptococcus neoformans / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000378:metabolism; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D007501:Iron / Q000378:metabolism; D008968:Molecular Conformation; D010587:Phagocytosis; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000946:Antigens, Fungal; D000939:Epitopes; D011134:Polysaccharides; D007501:Iron
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