NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/14925 |
Resumo: | C. parapsilosis infections incidence has been increasing for the past 20 years. Its caracteristics of adhering and forming biofilms are a critical factor for infection caused by this organism, affecting from immunocompromised or transplanted patients to low-birth-weight neonates. The health-care workers are a major transmission vehicle of this fungus. The azoles class of antifungal drugs are the first and most common line of defense to treat infections by this type of yeast species. Its mode of action on the yeast cell works by inhibiting the lanoststerol 14α-demethylase, an enzyme belonging to the ergosterol biosyntethic pathway.. On a recent study it has become clear that C. parapsilosis antifungal azole resistance may display similar resistance mechanisms that the ones described for C. albicans. A resistant strain obtained after exposure to posaconazole has shown an upregulation of two transcriptional factors, Upc2 and Ndt80. The aim of this work was to assess the role of these two transcriptional factors on C. parapsilosis azole resistance. For that, it was intended to knockout both genes using the SAT1-flipper cassette. The strain obtained after disruption of one copy of NDT80 gene displayed an unexpected phenotype, concerning adhesion and biofilm formation, comparatively to the wild-type BC014 strain. It were also made susceptibility tests although with no evident changes. These results demonstrate that NDT80 gene may be a negative regulator of C. parapsilosis adherence to abiotic and biotic substrates, impairing also biofilm formation. |
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NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formationBiologia molecularTranscrição genéticaBiofilmesCandida parapsilosisC. parapsilosis infections incidence has been increasing for the past 20 years. Its caracteristics of adhering and forming biofilms are a critical factor for infection caused by this organism, affecting from immunocompromised or transplanted patients to low-birth-weight neonates. The health-care workers are a major transmission vehicle of this fungus. The azoles class of antifungal drugs are the first and most common line of defense to treat infections by this type of yeast species. Its mode of action on the yeast cell works by inhibiting the lanoststerol 14α-demethylase, an enzyme belonging to the ergosterol biosyntethic pathway.. On a recent study it has become clear that C. parapsilosis antifungal azole resistance may display similar resistance mechanisms that the ones described for C. albicans. A resistant strain obtained after exposure to posaconazole has shown an upregulation of two transcriptional factors, Upc2 and Ndt80. The aim of this work was to assess the role of these two transcriptional factors on C. parapsilosis azole resistance. For that, it was intended to knockout both genes using the SAT1-flipper cassette. The strain obtained after disruption of one copy of NDT80 gene displayed an unexpected phenotype, concerning adhesion and biofilm formation, comparatively to the wild-type BC014 strain. It were also made susceptibility tests although with no evident changes. These results demonstrate that NDT80 gene may be a negative regulator of C. parapsilosis adherence to abiotic and biotic substrates, impairing also biofilm formation.As infecções por C. parapsilosis têm vindo a aumentar nos últimos 20 anos. As suas características intrínsecas de adesão e capacidade de formação de biofilmes são um factor critíco de infecção, sendo os pacientes transplantados ou com o sistema imunitário comprometido ou mesmo os neonatos de baixo peso o grupo de risco mais afectado. Os prestadores de cuidados de saúde são o meio de transmissão mais comum para a infecção por esta levedura. A classe dos antifúngicos azóis são a primeira linha de defesa para tratamento de infecções por este tipo de leveduras. Estes actuam inibindo a enzima lanosterol 14α-demethylase, enzima constituinte da via biossintética do ergosterol. Um estudo recente demonstrontrou que a resistência aos azoles em C. parapsilosis poderá ter os mesmos mecanismos observados e estudados em C. albicans. Uma estirpe resistente obtida após exposição a Posaconazole revelou uma sobre-expressão de 13 genes envolvidos na biossíntese do ergosterol, entre eles dois factores de transcrição, Upc2 e Ndt80. Com vista a avaliar o papel destes factores de transcrição na resistência aos azoles em C. parapsilosis, pretendeu-se efectuar a delecção dos dois genes usando a ferramenta molecular SAT1-flipper cassette. Apenas um alelo do gene NDT80 foi deletado, originando um fenótipo distinto em comparação com a estirpe original BC014, em particular na sua capacidade de adesão e de formação de biofilmes. Foram realizados testes de susceptibilidade embora sem qualquer diferença evidente entre fenótipos. Estes resultados demonstram que o gene NDT80 pode ser um regulador negativo da capacidade de adesão de C. parapsilosis, afectando também o seu potencial de formação de biofilmes.Universidade de Aveiro2015-12-04T14:36:04Z2014-01-01T00:00:00Z2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/14925TID:201588099engGomes, Nuno Miguel Araújo da Cunhainfo: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:RCAAP2024-02-22T11:27:27Zoai:ria.ua.pt:10773/14925Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:50:24.264322Repositório 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 |
NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation |
title |
NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation |
spellingShingle |
NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation Gomes, Nuno Miguel Araújo da Cunha Biologia molecular Transcrição genética Biofilmes Candida parapsilosis |
title_short |
NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation |
title_full |
NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation |
title_fullStr |
NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation |
title_full_unstemmed |
NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation |
title_sort |
NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation |
author |
Gomes, Nuno Miguel Araújo da Cunha |
author_facet |
Gomes, Nuno Miguel Araújo da Cunha |
author_role |
author |
dc.contributor.author.fl_str_mv |
Gomes, Nuno Miguel Araújo da Cunha |
dc.subject.por.fl_str_mv |
Biologia molecular Transcrição genética Biofilmes Candida parapsilosis |
topic |
Biologia molecular Transcrição genética Biofilmes Candida parapsilosis |
description |
C. parapsilosis infections incidence has been increasing for the past 20 years. Its caracteristics of adhering and forming biofilms are a critical factor for infection caused by this organism, affecting from immunocompromised or transplanted patients to low-birth-weight neonates. The health-care workers are a major transmission vehicle of this fungus. The azoles class of antifungal drugs are the first and most common line of defense to treat infections by this type of yeast species. Its mode of action on the yeast cell works by inhibiting the lanoststerol 14α-demethylase, an enzyme belonging to the ergosterol biosyntethic pathway.. On a recent study it has become clear that C. parapsilosis antifungal azole resistance may display similar resistance mechanisms that the ones described for C. albicans. A resistant strain obtained after exposure to posaconazole has shown an upregulation of two transcriptional factors, Upc2 and Ndt80. The aim of this work was to assess the role of these two transcriptional factors on C. parapsilosis azole resistance. For that, it was intended to knockout both genes using the SAT1-flipper cassette. The strain obtained after disruption of one copy of NDT80 gene displayed an unexpected phenotype, concerning adhesion and biofilm formation, comparatively to the wild-type BC014 strain. It were also made susceptibility tests although with no evident changes. These results demonstrate that NDT80 gene may be a negative regulator of C. parapsilosis adherence to abiotic and biotic substrates, impairing also biofilm formation. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-01-01T00:00:00Z 2014 2015-12-04T14:36:04Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/14925 TID:201588099 |
url |
http://hdl.handle.net/10773/14925 |
identifier_str_mv |
TID:201588099 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade de Aveiro |
publisher.none.fl_str_mv |
Universidade de Aveiro |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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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) |
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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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