Functional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>

ABSTRACT Candida parapsilosis is an emerging non-albicans Candida species that largely affects low-birth-weight infants and immunocompromised patients. Fungal pathogenesis is promoted by the dynamic expression of diverse virulence factors, with secreted proteolytic enzymes being linked to the establ...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Dhirendra Kumar Singh, Tibor Németh, Alexandra Papp, Renáta Tóth, Szilvia Lukácsi, Olga Heidingsfeld, Jiri Dostal, Csaba Vágvölgyi, Zsuzsa Bajtay, Mihály Józsi, Attila Gácser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Candida parapsilosis complement host-pathogen interactions proteases virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3eb509e7d500480e87cff835f4119c7e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3eb509e7d500480e87cff835f4119c7e
record_format	dspace
spelling	oai:doaj.org-article:3eb509e7d500480e87cff835f4119c7e2021-11-15T15:22:27ZFunctional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>10.1128/mSphere.00484-192379-5042https://doaj.org/article/3eb509e7d500480e87cff835f4119c7e2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00484-19https://doaj.org/toc/2379-5042ABSTRACT Candida parapsilosis is an emerging non-albicans Candida species that largely affects low-birth-weight infants and immunocompromised patients. Fungal pathogenesis is promoted by the dynamic expression of diverse virulence factors, with secreted proteolytic enzymes being linked to the establishment and progression of disease. Although secreted aspartyl proteases (Sap) are critical for Candida albicans pathogenicity, their role in C. parapsilosis is poorly elucidated. In the present study, we aimed to examine the contribution of C. parapsilosis SAPP genes SAPP1, SAPP2, and SAPP3 to the virulence of the species. Our results indicate that SAPP1 and SAPP2, but not SAPP3, influence adhesion, host cell damage, phagosome-lysosome maturation, phagocytosis, killing capacity, and cytokine secretion by human peripheral blood-derived macrophages. Purified Sapp1p and Sapp2p were also shown to efficiently cleave host complement component 3b (C3b) and C4b proteins and complement regulator factor H. Additionally, Sapp2p was able to cleave factor H-related protein 5 (FHR-5). Altogether, these data demonstrate the diverse, significant contributions that SAPP1 and SAPP2 make to the establishment and progression of disease by C. parapsilosis through enabling the attachment of the yeast cells to mammalian cells and modulating macrophage biology and disruption of the complement cascade. IMPORTANCE Aspartyl proteases are present in various organisms and, among virulent species, are considered major virulence factors. Host tissue and cell damage, hijacking of immune responses, and hiding from innate immune cells are the most common behaviors of fungal secreted proteases enabling pathogen survival and invasion. C. parapsilosis, an opportunistic human-pathogenic fungus mainly threatening low-birth weight neonates and children, possesses three SAPP protein-encoding genes that could contribute to the invasiveness of the species. Our results suggest that SAPP1 and SAPP2, but not SAPP3, influence host evasion by regulating cell damage, phagocytosis, phagosome-lysosome maturation, killing, and cytokine secretion. Furthermore, SAPP1 and SAPP2 also effectively contribute to complement evasion.Dhirendra Kumar SinghTibor NémethAlexandra PappRenáta TóthSzilvia LukácsiOlga HeidingsfeldJiri DostalCsaba VágvölgyiZsuzsa BajtayMihály JózsiAttila GácserAmerican Society for MicrobiologyarticleCandida parapsilosiscomplementhost-pathogen interactionsproteasesvirulenceMicrobiologyQR1-502ENmSphere, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida parapsilosis complement host-pathogen interactions proteases virulence Microbiology QR1-502
spellingShingle	Candida parapsilosis complement host-pathogen interactions proteases virulence Microbiology QR1-502 Dhirendra Kumar Singh Tibor Németh Alexandra Papp Renáta Tóth Szilvia Lukácsi Olga Heidingsfeld Jiri Dostal Csaba Vágvölgyi Zsuzsa Bajtay Mihály Józsi Attila Gácser Functional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>
description	ABSTRACT Candida parapsilosis is an emerging non-albicans Candida species that largely affects low-birth-weight infants and immunocompromised patients. Fungal pathogenesis is promoted by the dynamic expression of diverse virulence factors, with secreted proteolytic enzymes being linked to the establishment and progression of disease. Although secreted aspartyl proteases (Sap) are critical for Candida albicans pathogenicity, their role in C. parapsilosis is poorly elucidated. In the present study, we aimed to examine the contribution of C. parapsilosis SAPP genes SAPP1, SAPP2, and SAPP3 to the virulence of the species. Our results indicate that SAPP1 and SAPP2, but not SAPP3, influence adhesion, host cell damage, phagosome-lysosome maturation, phagocytosis, killing capacity, and cytokine secretion by human peripheral blood-derived macrophages. Purified Sapp1p and Sapp2p were also shown to efficiently cleave host complement component 3b (C3b) and C4b proteins and complement regulator factor H. Additionally, Sapp2p was able to cleave factor H-related protein 5 (FHR-5). Altogether, these data demonstrate the diverse, significant contributions that SAPP1 and SAPP2 make to the establishment and progression of disease by C. parapsilosis through enabling the attachment of the yeast cells to mammalian cells and modulating macrophage biology and disruption of the complement cascade. IMPORTANCE Aspartyl proteases are present in various organisms and, among virulent species, are considered major virulence factors. Host tissue and cell damage, hijacking of immune responses, and hiding from innate immune cells are the most common behaviors of fungal secreted proteases enabling pathogen survival and invasion. C. parapsilosis, an opportunistic human-pathogenic fungus mainly threatening low-birth weight neonates and children, possesses three SAPP protein-encoding genes that could contribute to the invasiveness of the species. Our results suggest that SAPP1 and SAPP2, but not SAPP3, influence host evasion by regulating cell damage, phagocytosis, phagosome-lysosome maturation, killing, and cytokine secretion. Furthermore, SAPP1 and SAPP2 also effectively contribute to complement evasion.
format	article
author	Dhirendra Kumar Singh Tibor Németh Alexandra Papp Renáta Tóth Szilvia Lukácsi Olga Heidingsfeld Jiri Dostal Csaba Vágvölgyi Zsuzsa Bajtay Mihály Józsi Attila Gácser
author_facet	Dhirendra Kumar Singh Tibor Németh Alexandra Papp Renáta Tóth Szilvia Lukácsi Olga Heidingsfeld Jiri Dostal Csaba Vágvölgyi Zsuzsa Bajtay Mihály Józsi Attila Gácser
author_sort	Dhirendra Kumar Singh
title	Functional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>
title_short	Functional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>
title_full	Functional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>
title_fullStr	Functional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>
title_full_unstemmed	Functional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>
title_sort	functional characterization of secreted aspartyl proteases in <named-content content-type="genus-species">candida parapsilosis</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/3eb509e7d500480e87cff835f4119c7e
work_keys_str_mv	AT dhirendrakumarsingh functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT tibornemeth functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT alexandrapapp functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT renatatoth functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT szilvialukacsi functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT olgaheidingsfeld functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT jiridostal functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT csabavagvolgyi functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT zsuzsabajtay functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT mihalyjozsi functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent AT attilagacser functionalcharacterizationofsecretedaspartylproteasesinnamedcontentcontenttypegenusspeciescandidaparapsilosisnamedcontent
_version_	1718427942642515968

Functional Characterization of Secreted Aspartyl Proteases in <named-content content-type="genus-species">Candida parapsilosis</named-content>

Ejemplares similares