Probert, M., Zhou, X., Goodall, M. et al. (4 more authors) (2019) A glucuronoxylomannan epitope exhibits serotype-specific accessibility and redistributes towards the capsule surface during Titanisation of the fungal pathogen Cryptococcus neoformans. Infection and Immunity, 87 (4). e00731-18. ISSN 0019-9567
Abstract
Disseminated infections with the fungal species Cryptococcus neoformans or, less frequently, C. 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 antigen. 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 characterisation of a novel anti-GXM mAb, Crp127, that unexpectedly reveals a role for GXM remodelling during the process of fungal Titanisation. We show that Crp127 recognises 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 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 characterised morphotype where haploid 5 μm cells convert to highly polyploid cells >10 μm with distinct but poorly understood capsular characteristics. Titans 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 American Society for Microbiology. This is an author produced version of a paper subsequently published in Infection and Immunity. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Feb 2019 13:27 |
Last Modified: | 17 Nov 2021 09:39 |
Status: | Published |
Publisher: | American Society for Microbiology |
Refereed: | Yes |
Identification Number: | 10.1128/IAI.00731-18 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:142051 |