Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/37210 |
Resumo: | Candida glabrata is considered a major opportunistic fungal pathogen of humans. The capacity of this yeast species to cause infections is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources, such as carboxylic acids, contributes to the virulence of this fungus. Transcriptional studies on C. glabrata cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analysing biofilm formation, antifungal drug resistance and phagocytosis of C. glabrata cells grown in the presence of acetic acid as an alternative carbon source. C. glabrata planktonic cells grown in media containing acetic acid were more susceptible to fluconazole and were better phagocytosed and killed by macrophages than when compared to media lacking acetic acid. Growth in acetic acid also affected the ability of C. glabrata to form biofilms. The genes ADY2a, ADY2b, FPS1, FPS2 and ATO3, encoding putative carboxylate transporters, were upregulated in C. glabrata planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with fps1 and ady2a mutant strains suggested a potential role of FPS1 and ADY2a in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of C. glabrata infections, in particular in vaginal candidiasis. |
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Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetateCandida glabrataAcetateTransportersPhagocytosisAntifungal drug resistanceFluconazoleCandidiasisCiências Médicas::Biotecnologia MédicaScience & TechnologyCandida glabrata is considered a major opportunistic fungal pathogen of humans. The capacity of this yeast species to cause infections is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources, such as carboxylic acids, contributes to the virulence of this fungus. Transcriptional studies on C. glabrata cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analysing biofilm formation, antifungal drug resistance and phagocytosis of C. glabrata cells grown in the presence of acetic acid as an alternative carbon source. C. glabrata planktonic cells grown in media containing acetic acid were more susceptible to fluconazole and were better phagocytosed and killed by macrophages than when compared to media lacking acetic acid. Growth in acetic acid also affected the ability of C. glabrata to form biofilms. The genes ADY2a, ADY2b, FPS1, FPS2 and ATO3, encoding putative carboxylate transporters, were upregulated in C. glabrata planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with fps1 and ady2a mutant strains suggested a potential role of FPS1 and ADY2a in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of C. glabrata infections, in particular in vaginal candidiasis.Portuguese grant PTDC/SAU- MIC/119069/2010. SM received FCT PhD fellowship (SFRH/ BD/ 74790/ 2010). The work on CBMA was supported by FEDER through POFC-COMPETE, by FCT I.P. through the strategic funding UID/BIA/04050/2013 and by FCT through grant PEst-OE/BIA/UI4050/2014. FLU were kindly provided by Pfizer R , S.A. in its pure compound form. The work on CEB was supported by PEst-OE/EQB/LA0023/2013, from FCT, “BioHealth – Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER and the project “Consolidating Research Expert ise and Resources on Cellular and Molecular Biotechnology at CEB/IBB”, Ref. FCOMP-01-0124- FEDER-027462. We also would like to acknowledge the support of the European Research Council through the advanced grant “STRIFE” (C-2009-AdG-249793).Frontiers MediaUniversidade do MinhoMota, SandraAlves, RosanaCarneiro, CatarinaSilva, Sónia CarinaBrown, Alistair J.Istel, FabianKuchler, KarlSampaio, PaulaCasal, MargaridaHenriques, MarianaPaiva, Sandra2015-092015-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/37210engMota, Sandra; Alves, Rosana; Carneiro, Catarina; Silva, Sónia; Brown, Alistair J.; Istel, Fabian; Kuchler, Karl; Sampaio, Paula; Casal, Margarida; Henriques, Mariana; Paiva, Sandra, Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate. Frontiers in Microbiology, 6(919), 20151664-302X10.3389/fmicb.2015.00919http://journal.frontiersin.org/article/10.3389/fmicb.2015.00919/abstractinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:43:59Zoai:repositorium.sdum.uminho.pt:1822/37210Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:41:35.272321Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate |
title |
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate |
spellingShingle |
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate Mota, Sandra Candida glabrata Acetate Transporters Phagocytosis Antifungal drug resistance Fluconazole Candidiasis Ciências Médicas::Biotecnologia Médica Science & Technology |
title_short |
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate |
title_full |
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate |
title_fullStr |
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate |
title_full_unstemmed |
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate |
title_sort |
Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate |
author |
Mota, Sandra |
author_facet |
Mota, Sandra Alves, Rosana Carneiro, Catarina Silva, Sónia Carina Brown, Alistair J. Istel, Fabian Kuchler, Karl Sampaio, Paula Casal, Margarida Henriques, Mariana Paiva, Sandra |
author_role |
author |
author2 |
Alves, Rosana Carneiro, Catarina Silva, Sónia Carina Brown, Alistair J. Istel, Fabian Kuchler, Karl Sampaio, Paula Casal, Margarida Henriques, Mariana Paiva, Sandra |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Mota, Sandra Alves, Rosana Carneiro, Catarina Silva, Sónia Carina Brown, Alistair J. Istel, Fabian Kuchler, Karl Sampaio, Paula Casal, Margarida Henriques, Mariana Paiva, Sandra |
dc.subject.por.fl_str_mv |
Candida glabrata Acetate Transporters Phagocytosis Antifungal drug resistance Fluconazole Candidiasis Ciências Médicas::Biotecnologia Médica Science & Technology |
topic |
Candida glabrata Acetate Transporters Phagocytosis Antifungal drug resistance Fluconazole Candidiasis Ciências Médicas::Biotecnologia Médica Science & Technology |
description |
Candida glabrata is considered a major opportunistic fungal pathogen of humans. The capacity of this yeast species to cause infections is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources, such as carboxylic acids, contributes to the virulence of this fungus. Transcriptional studies on C. glabrata cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analysing biofilm formation, antifungal drug resistance and phagocytosis of C. glabrata cells grown in the presence of acetic acid as an alternative carbon source. C. glabrata planktonic cells grown in media containing acetic acid were more susceptible to fluconazole and were better phagocytosed and killed by macrophages than when compared to media lacking acetic acid. Growth in acetic acid also affected the ability of C. glabrata to form biofilms. The genes ADY2a, ADY2b, FPS1, FPS2 and ATO3, encoding putative carboxylate transporters, were upregulated in C. glabrata planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with fps1 and ady2a mutant strains suggested a potential role of FPS1 and ADY2a in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of C. glabrata infections, in particular in vaginal candidiasis. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-09 2015-09-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/37210 |
url |
http://hdl.handle.net/1822/37210 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Mota, Sandra; Alves, Rosana; Carneiro, Catarina; Silva, Sónia; Brown, Alistair J.; Istel, Fabian; Kuchler, Karl; Sampaio, Paula; Casal, Margarida; Henriques, Mariana; Paiva, Sandra, Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate. Frontiers in Microbiology, 6(919), 2015 1664-302X 10.3389/fmicb.2015.00919 http://journal.frontiersin.org/article/10.3389/fmicb.2015.00919/abstract |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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