Allergen1 regulates polysaccharide structure in Cryptococcus neoformans

Authors

  • Neena Jain,

    1. Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, 10461, USA
    2. Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, 10461, USA
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    • Authors contributed equally to this work.
  • Radames J. B. Cordero,

    1. Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, 10461, USA
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    • Authors contributed equally to this work.
  • Arturo Casadevall,

    1. Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, 10461, USA
    2. Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, 10461, USA
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  • Bettina C. Fries

    Corresponding author
    1. Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, 10461, USA
    • Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, 10461, USA
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For correspondence. E-mail bettina.fries@einstein.yu.edu; Tel. (+1) 718 430 2365; Fax (+1) 718 430 8968.

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.

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