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

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A glucuronoxylomannan epitope exhibits serotype-specific accessibility and redistributes towards the capsule surface during titanization of the fungal pathogen Cryptococcus neoformans. / Probert, Mark; Zhou, Xin; Goodall, Margaret; Johnston, Simon; Bielska, Ewa; Ballou, Elizabeth R; May, Robin.

In: Infection and Immunity, Vol. 87, No. 4, e00731, 04.2019.

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@article{203cd292e9cd441fa4784ef439c99144,
title = "A glucuronoxylomannan epitope exhibits serotype-specific accessibility and redistributes towards the capsule surface during titanization of the fungal pathogen Cryptococcus neoformans",
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. ",
keywords = "Cryptococcus, Antibody, Capsule, antibody, Fungal, Pathogen",
author = "Mark Probert and Xin Zhou and Margaret Goodall and Simon Johnston and Ewa Bielska and Ballou, {Elizabeth R} and Robin May",
note = "Copyright {\textcopyright} 2019 American Society for Microbiology.",
year = "2019",
month = apr,
doi = "10.1128/IAI.00731-18",
language = "English",
volume = "87",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "4",

}

RIS

TY - JOUR

T1 - A glucuronoxylomannan epitope exhibits serotype-specific accessibility and redistributes towards the capsule surface during titanization of the fungal pathogen Cryptococcus neoformans

AU - Probert, Mark

AU - Zhou, Xin

AU - Goodall, Margaret

AU - Johnston, Simon

AU - Bielska, Ewa

AU - Ballou, Elizabeth R

AU - May, Robin

N1 - Copyright © 2019 American Society for Microbiology.

PY - 2019/4

Y1 - 2019/4

N2 - 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.

AB - 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.

KW - Cryptococcus

KW - Antibody

KW - Capsule

KW - antibody

KW - Fungal

KW - Pathogen

UR - http://www.scopus.com/inward/record.url?scp=85063713263&partnerID=8YFLogxK

U2 - 10.1128/IAI.00731-18

DO - 10.1128/IAI.00731-18

M3 - Article

C2 - 30670549

VL - 87

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 4

M1 - e00731

ER -