The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.

Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. Calcium homeostasis and signaling is essential for numerous biological processes and also influences A. fumigatus pathogenicity. The presented study characterized the function of the A. fumigatus homologues of three Sac...

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Autores principales:	Patrícia Alves de Castro, Jéssica Chiaratto, Lizziane K Winkelströter, Vinícius Leite Pedro Bom, Leandra Naira Zambelli Ramalho, Maria Helena S Goldman, Neil Andrew Brown, Gustavo H Goldman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2bfdfa47ae664b0aa46ee5c621be1f90
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spelling	oai:doaj.org-article:2bfdfa47ae664b0aa46ee5c621be1f902021-11-25T06:06:25ZThe involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.1932-620310.1371/journal.pone.0103957https://doaj.org/article/2bfdfa47ae664b0aa46ee5c621be1f902014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25083783/?tool=EBIhttps://doaj.org/toc/1932-6203Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. Calcium homeostasis and signaling is essential for numerous biological processes and also influences A. fumigatus pathogenicity. The presented study characterized the function of the A. fumigatus homologues of three Saccharomyces cerevisiae calcium channels, voltage-gated Cch1, stretch-activated Mid1 and vacuolar Yvc1. The A. fumigatus calcium channels cchA, midA and yvcA were regulated at transcriptional level by increased calcium levels. The YvcA::GFP fusion protein localized to the vacuoles. Both ΔcchA and ΔmidA mutant strains showed reduced radial growth rate in nutrient-poor minimal media. Interestingly, this growth defect in the ΔcchA strain was rescued by the exogenous addition of CaCl2. The ΔcchA, ΔmidA, and ΔcchA ΔmidA strains were also sensitive to the oxidative stress inducer, paraquat. Restriction of external Ca(2+) through the addition of the Ca(2+)-chelator EGTA impacted upon the growth of the ΔcchA and ΔmidA strains. All the A. fumigatus ΔcchA, ΔmidA, and ΔyvcA strains demonstrated attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Infection with the parental strain resulted in a 100% mortality rate at 15 days post-infection, while the mortality rate of the ΔcchA, ΔmidA, and ΔyvcA strains after 15 days post-infection was only 25%. Collectively, this investigation strongly indicates that CchA, MidA, and YvcA play a role in A. fumigatus calcium homeostasis and virulence.Patrícia Alves de CastroJéssica ChiarattoLizziane K WinkelströterVinícius Leite Pedro BomLeandra Naira Zambelli RamalhoMaria Helena S GoldmanNeil Andrew BrownGustavo H GoldmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e103957 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patrícia Alves de Castro Jéssica Chiaratto Lizziane K Winkelströter Vinícius Leite Pedro Bom Leandra Naira Zambelli Ramalho Maria Helena S Goldman Neil Andrew Brown Gustavo H Goldman The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.
description	Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. Calcium homeostasis and signaling is essential for numerous biological processes and also influences A. fumigatus pathogenicity. The presented study characterized the function of the A. fumigatus homologues of three Saccharomyces cerevisiae calcium channels, voltage-gated Cch1, stretch-activated Mid1 and vacuolar Yvc1. The A. fumigatus calcium channels cchA, midA and yvcA were regulated at transcriptional level by increased calcium levels. The YvcA::GFP fusion protein localized to the vacuoles. Both ΔcchA and ΔmidA mutant strains showed reduced radial growth rate in nutrient-poor minimal media. Interestingly, this growth defect in the ΔcchA strain was rescued by the exogenous addition of CaCl2. The ΔcchA, ΔmidA, and ΔcchA ΔmidA strains were also sensitive to the oxidative stress inducer, paraquat. Restriction of external Ca(2+) through the addition of the Ca(2+)-chelator EGTA impacted upon the growth of the ΔcchA and ΔmidA strains. All the A. fumigatus ΔcchA, ΔmidA, and ΔyvcA strains demonstrated attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Infection with the parental strain resulted in a 100% mortality rate at 15 days post-infection, while the mortality rate of the ΔcchA, ΔmidA, and ΔyvcA strains after 15 days post-infection was only 25%. Collectively, this investigation strongly indicates that CchA, MidA, and YvcA play a role in A. fumigatus calcium homeostasis and virulence.
format	article
author	Patrícia Alves de Castro Jéssica Chiaratto Lizziane K Winkelströter Vinícius Leite Pedro Bom Leandra Naira Zambelli Ramalho Maria Helena S Goldman Neil Andrew Brown Gustavo H Goldman
author_facet	Patrícia Alves de Castro Jéssica Chiaratto Lizziane K Winkelströter Vinícius Leite Pedro Bom Leandra Naira Zambelli Ramalho Maria Helena S Goldman Neil Andrew Brown Gustavo H Goldman
author_sort	Patrícia Alves de Castro
title	The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.
title_short	The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.
title_full	The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.
title_fullStr	The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.
title_full_unstemmed	The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.
title_sort	involvement of the mid1/cch1/yvc1 calcium channels in aspergillus fumigatus virulence.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2bfdfa47ae664b0aa46ee5c621be1f90
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The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.

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