Allergen1 regulates polysaccharide structure in Cryptococcus neoformans

Neena Jain, Radames J.B. Cordero, Arturo Casadevall, Bettina C. Fries

Research output: Contribution to journalArticlepeer-review

Abstract

Summary: 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.

Original languageEnglish (US)
Pages (from-to)713-727
Number of pages15
JournalMolecular Microbiology
Volume88
Issue number4
DOIs
StatePublished - May 2013
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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