A glucuronoxylomannan epitope exhibits serotype-specific accessibility and redistributes towards the capsule surface during titanization of the fungal pathogen Cryptococcus neoformans

Research output: Contribution to journalArticle

Authors

  • Mark Probert
  • Xin Zhou
  • Margaret Goodall
  • Simon Johnston
  • Elizabeth R Ballou

Colleges, School and Institutes

External organisations

  • Institute of Microbiology and Infection, School of Biosciences, University of BirminghamBirmingham, United Kingdom.
  • Institute of Immunology & Immunotherapy, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK
  • University of Sheffield

Abstract

Disseminated infections with the fungal species Cryptococcus neoformans or, less frequently, Cryptococcus gattii are an important cause of mortality in immunocompromised individuals. Central to the virulence of both species is an elaborate polysaccharide capsule that consists predominantly of glucuronoxylomannan (GXM). Due to its abundance, GXM is an ideal target for host antibodies, and several monoclonal antibodies (mAbs) have previously been derived using purified GXM or whole capsular preparations as antigens. In addition to their application in the diagnosis of cryptococcosis, anti-GXM mAbs are invaluable tools for studying capsule structure. In this study, we report the production and characterization of a novel anti-GXM mAb, Crp127, that unexpectedly reveals a role for GXM remodeling during the process of fungal titanization. We show that Crp127 recognizes a GXM epitope in an O-acetylation-dependent, but xylosylation-independent, manner. The epitope is differentially expressed by the four main serotypes of Cryptococcus neoformans and C. gattii, is heterogeneously expressed within clonal populations of C. gattii serotype B strains, and is typically confined to the central region of the enlarged capsule. Uniquely, however, this epitope redistributes to the capsular surface in titan cells, a recently characterized morphotype where haploid 5-μm cells convert to highly polyploid cells of >10 μm with distinct but poorly understood capsular characteristics. Titan cells are produced in the host lung and critical for successful infection. Crp127 therefore advances our understanding of cryptococcal morphological change and may hold significant potential as a tool to differentially identify cryptococcal strains and subtypes.

Bibliographic note

Copyright © 2019 American Society for Microbiology.

Details

Original languageEnglish
Article numbere00731
Number of pages18
JournalInfection and Immunity
Volume87
Issue number4
Early online date25 Mar 2019
Publication statusPublished - Apr 2019

Keywords

  • Cryptococcus, Antibody, Capsule, antibody, Fungal, Pathogen