Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition

Abstract Candida albicans is an opportunistic fungal pathogen colonizing the oral cavity. C. albicans secreted aspartic protease Sap6 is important for virulence during oral candidiasis since it degrades host tissues to release nutrients and essential transition metals. We found that zinc specificall...

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Autores principales:	Rohitashw Kumar, Christine Breindel, Darpan Saraswat, Paul J. Cullen, Mira Edgerton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15ddcf2dabd446da987100c3ae3d6c49
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spelling	oai:doaj.org-article:15ddcf2dabd446da987100c3ae3d6c492021-12-02T11:52:15ZCandida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition10.1038/s41598-017-03082-42045-2322https://doaj.org/article/15ddcf2dabd446da987100c3ae3d6c492017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03082-4https://doaj.org/toc/2045-2322Abstract Candida albicans is an opportunistic fungal pathogen colonizing the oral cavity. C. albicans secreted aspartic protease Sap6 is important for virulence during oral candidiasis since it degrades host tissues to release nutrients and essential transition metals. We found that zinc specifically increased C. albicans autoaggregation induced by Sap6; and that Sap6 itself bound zinc ions. In silico analysis of Sap6 predicted four amyloidogenic regions that were synthesized as peptides (P1–P4). All peptides, as well as full length Sap6, demonstrated amyloid properties, and addition of zinc further increased amyloid formation. Disruption of amyloid regions by Congo red significantly reduced auotoaggregation. Deletion of C. albicans genes that control zinc acquisition in the ZAP1 regulon, including zinc transporters (Pra1 and Zrt1) and other zinc-regulated surface proteins, resulted in lower autoaggregation and reduction of surface binding of Sap6. Cells with high expression of PRA1 and ZRT1 also showed increased Sap6-mediated autoaggregation. C. albicans ∆sap6 deletion mutants failed to accumulate intracellular zinc comparable to ∆zap1, ∆zrt1, and ∆pra1 cells. Thus Sap6 is a multi-functional molecule containing amyloid regions that promotes autoaggregation and zinc uptake, and may serve as an additional system for the community acquisition of zinc.Rohitashw KumarChristine BreindelDarpan SaraswatPaul J. CullenMira EdgertonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rohitashw Kumar Christine Breindel Darpan Saraswat Paul J. Cullen Mira Edgerton Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition
description	Abstract Candida albicans is an opportunistic fungal pathogen colonizing the oral cavity. C. albicans secreted aspartic protease Sap6 is important for virulence during oral candidiasis since it degrades host tissues to release nutrients and essential transition metals. We found that zinc specifically increased C. albicans autoaggregation induced by Sap6; and that Sap6 itself bound zinc ions. In silico analysis of Sap6 predicted four amyloidogenic regions that were synthesized as peptides (P1–P4). All peptides, as well as full length Sap6, demonstrated amyloid properties, and addition of zinc further increased amyloid formation. Disruption of amyloid regions by Congo red significantly reduced auotoaggregation. Deletion of C. albicans genes that control zinc acquisition in the ZAP1 regulon, including zinc transporters (Pra1 and Zrt1) and other zinc-regulated surface proteins, resulted in lower autoaggregation and reduction of surface binding of Sap6. Cells with high expression of PRA1 and ZRT1 also showed increased Sap6-mediated autoaggregation. C. albicans ∆sap6 deletion mutants failed to accumulate intracellular zinc comparable to ∆zap1, ∆zrt1, and ∆pra1 cells. Thus Sap6 is a multi-functional molecule containing amyloid regions that promotes autoaggregation and zinc uptake, and may serve as an additional system for the community acquisition of zinc.
format	article
author	Rohitashw Kumar Christine Breindel Darpan Saraswat Paul J. Cullen Mira Edgerton
author_facet	Rohitashw Kumar Christine Breindel Darpan Saraswat Paul J. Cullen Mira Edgerton
author_sort	Rohitashw Kumar
title	Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition
title_short	Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition
title_full	Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition
title_fullStr	Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition
title_full_unstemmed	Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition
title_sort	candida albicans sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/15ddcf2dabd446da987100c3ae3d6c49
work_keys_str_mv	AT rohitashwkumar candidaalbicanssap6amyloidregionsfunctionincellularaggregationandzincbindingandcontributetozincacquisition AT christinebreindel candidaalbicanssap6amyloidregionsfunctionincellularaggregationandzincbindingandcontributetozincacquisition AT darpansaraswat candidaalbicanssap6amyloidregionsfunctionincellularaggregationandzincbindingandcontributetozincacquisition AT pauljcullen candidaalbicanssap6amyloidregionsfunctionincellularaggregationandzincbindingandcontributetozincacquisition AT miraedgerton candidaalbicanssap6amyloidregionsfunctionincellularaggregationandzincbindingandcontributetozincacquisition
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Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition

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