A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.

Polysaccharide capsules are important virulence factors for many microbial pathogens including the opportunistic fungus Cryptococcus neoformans. In the present study, we demonstrate an unusual role for a secreted lactonohydrolase of C. neoformans, LHC1 in capsular higher order structure. Analysis of...

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Autores principales: Yoon-Dong Park, Soowan Shin, John Panepinto, Jeanie Ramos, Jin Qiu, Susana Frases, Patricia Albuquerque, Radames J B Cordero, Nannan Zhang, Uwe Himmelreich, David Beenhouwer, John E Bennett, Arturo Casadevall, Peter R Williamson
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Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/ac9671a3a9724e458af31c7416bab8f3
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spelling oai:doaj.org-article:ac9671a3a9724e458af31c7416bab8f32021-11-18T06:06:39ZA role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.1553-73661553-737410.1371/journal.ppat.1004037https://doaj.org/article/ac9671a3a9724e458af31c7416bab8f32014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24789368/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Polysaccharide capsules are important virulence factors for many microbial pathogens including the opportunistic fungus Cryptococcus neoformans. In the present study, we demonstrate an unusual role for a secreted lactonohydrolase of C. neoformans, LHC1 in capsular higher order structure. Analysis of extracted capsular polysaccharide from wild-type and lhc1Δ strains by dynamic and static light scattering suggested a role for the LHC1 locus in altering the capsular polysaccharide, both reducing dimensions and altering its branching, density and solvation. These changes in the capsular structure resulted in LHC1-dependent alterations of antibody binding patterns, reductions in human and mouse complement binding and phagocytosis by the macrophage-like cell line J774, as well as increased virulence in mice. These findings identify a unique molecular mechanism for tertiary structural changes in a microbial capsule, facilitating immune evasion and virulence of a fungal pathogen.Yoon-Dong ParkSoowan ShinJohn PanepintoJeanie RamosJin QiuSusana FrasesPatricia AlbuquerqueRadames J B CorderoNannan ZhangUwe HimmelreichDavid BeenhouwerJohn E BennettArturo CasadevallPeter R WilliamsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 5, p e1004037 (2014)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Yoon-Dong Park
Soowan Shin
John Panepinto
Jeanie Ramos
Jin Qiu
Susana Frases
Patricia Albuquerque
Radames J B Cordero
Nannan Zhang
Uwe Himmelreich
David Beenhouwer
John E Bennett
Arturo Casadevall
Peter R Williamson
A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.
description Polysaccharide capsules are important virulence factors for many microbial pathogens including the opportunistic fungus Cryptococcus neoformans. In the present study, we demonstrate an unusual role for a secreted lactonohydrolase of C. neoformans, LHC1 in capsular higher order structure. Analysis of extracted capsular polysaccharide from wild-type and lhc1Δ strains by dynamic and static light scattering suggested a role for the LHC1 locus in altering the capsular polysaccharide, both reducing dimensions and altering its branching, density and solvation. These changes in the capsular structure resulted in LHC1-dependent alterations of antibody binding patterns, reductions in human and mouse complement binding and phagocytosis by the macrophage-like cell line J774, as well as increased virulence in mice. These findings identify a unique molecular mechanism for tertiary structural changes in a microbial capsule, facilitating immune evasion and virulence of a fungal pathogen.
format article
author Yoon-Dong Park
Soowan Shin
John Panepinto
Jeanie Ramos
Jin Qiu
Susana Frases
Patricia Albuquerque
Radames J B Cordero
Nannan Zhang
Uwe Himmelreich
David Beenhouwer
John E Bennett
Arturo Casadevall
Peter R Williamson
author_facet Yoon-Dong Park
Soowan Shin
John Panepinto
Jeanie Ramos
Jin Qiu
Susana Frases
Patricia Albuquerque
Radames J B Cordero
Nannan Zhang
Uwe Himmelreich
David Beenhouwer
John E Bennett
Arturo Casadevall
Peter R Williamson
author_sort Yoon-Dong Park
title A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.
title_short A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.
title_full A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.
title_fullStr A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.
title_full_unstemmed A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.
title_sort role for lhc1 in higher order structure and complement binding of the cryptococcus neoformans capsule.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/ac9671a3a9724e458af31c7416bab8f3
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