Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell
Autor(a) principal: | |
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Data de Publicação: | 2016 |
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/10400.5/13716 |
Resumo: | Blad polypeptide comprises residues 109–281 of Lupinus albus b-conglutin precursor. It occurs naturally as a major subunit of an edible, 210 kDa oligomer which accumulates to high levels, exclusively in the cotyledons of Lupinus seedlings between the 4th and 14th day after the onset of germination. Blad-containing oligomer (BCO) exhibits a potent and broad spectrum fungicide activity toward plant pathogens and is now on sale in the US under the tradename FractureTM. In this work we demonstrate its antifungal activity toward human pathogens and provide some insights on its mode of action. BCO bioactivity was evaluated in eight yeast species and compared to that of amphotericin B (AMB). BCO behaved similarly to AMB in what concerns both cellular inhibition and cellular death. As a lectin, BCO binds strongly to chitin. In addition, BCO is known to possess ‘exochitinase’ and ‘endochitosanase’ activities. However, no clear disruption was visualized at the cell wall after exposure to a lethal BCO concentration, except in cell buds. Immunofluorescent and immunogold labeling clearly indicate that BCO enters the cell, and membrane destabilization was also demonstrated. The absence of haemolytic activity, its biological origin, and its extraordinary antifungal activity are the major outcomes of this work, and provide a solid background for a future application as a new antifungal therapeutic drug. Furthermore, its predictable multisite mode of action suggests a low risk of inducing resistance mechanisms, which are now a major problem with other currently available antifungal drugs. |
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Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cellCandida albicansantifungalnatural productpathogenic yeastprotein-basedBlad polypeptide comprises residues 109–281 of Lupinus albus b-conglutin precursor. It occurs naturally as a major subunit of an edible, 210 kDa oligomer which accumulates to high levels, exclusively in the cotyledons of Lupinus seedlings between the 4th and 14th day after the onset of germination. Blad-containing oligomer (BCO) exhibits a potent and broad spectrum fungicide activity toward plant pathogens and is now on sale in the US under the tradename FractureTM. In this work we demonstrate its antifungal activity toward human pathogens and provide some insights on its mode of action. BCO bioactivity was evaluated in eight yeast species and compared to that of amphotericin B (AMB). BCO behaved similarly to AMB in what concerns both cellular inhibition and cellular death. As a lectin, BCO binds strongly to chitin. In addition, BCO is known to possess ‘exochitinase’ and ‘endochitosanase’ activities. However, no clear disruption was visualized at the cell wall after exposure to a lethal BCO concentration, except in cell buds. Immunofluorescent and immunogold labeling clearly indicate that BCO enters the cell, and membrane destabilization was also demonstrated. The absence of haemolytic activity, its biological origin, and its extraordinary antifungal activity are the major outcomes of this work, and provide a solid background for a future application as a new antifungal therapeutic drug. Furthermore, its predictable multisite mode of action suggests a low risk of inducing resistance mechanisms, which are now a major problem with other currently available antifungal drugs.Maria Tereza dos Santos Correia (ed.)Repositório da Universidade de LisboaPinheiro, Ana M.Carreira, AlexandraRollo, FilipeFernandes, RuiFerreira, Ricardo BoavidaMonteiro, Sara A.2017-06-05T14:49:13Z20162016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.5/13716engPinheiro AM, Carreira A, Rollo F, Fernandes R, Ferreira RB and Monteiro SA (2016) Blad-Containing Oligomer Fungicidal Activity on Human Pathogenic Yeasts. From the Outside to the Inside of the Target Cell. Front. Microbiol. 7:1803.10.3389/fmicb.2016.01803info: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:RCAAP2023-03-06T14:43:48Zoai:www.repository.utl.pt:10400.5/13716Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:59:39.691116Repositório 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 |
Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell |
title |
Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell |
spellingShingle |
Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell Pinheiro, Ana M. Candida albicans antifungal natural product pathogenic yeast protein-based |
title_short |
Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell |
title_full |
Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell |
title_fullStr |
Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell |
title_full_unstemmed |
Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell |
title_sort |
Blad-containing oligomer fungicidal activity on human pathogenic yeasts. From the outside to the inside of the target cell |
author |
Pinheiro, Ana M. |
author_facet |
Pinheiro, Ana M. Carreira, Alexandra Rollo, Filipe Fernandes, Rui Ferreira, Ricardo Boavida Monteiro, Sara A. |
author_role |
author |
author2 |
Carreira, Alexandra Rollo, Filipe Fernandes, Rui Ferreira, Ricardo Boavida Monteiro, Sara A. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Pinheiro, Ana M. Carreira, Alexandra Rollo, Filipe Fernandes, Rui Ferreira, Ricardo Boavida Monteiro, Sara A. |
dc.subject.por.fl_str_mv |
Candida albicans antifungal natural product pathogenic yeast protein-based |
topic |
Candida albicans antifungal natural product pathogenic yeast protein-based |
description |
Blad polypeptide comprises residues 109–281 of Lupinus albus b-conglutin precursor. It occurs naturally as a major subunit of an edible, 210 kDa oligomer which accumulates to high levels, exclusively in the cotyledons of Lupinus seedlings between the 4th and 14th day after the onset of germination. Blad-containing oligomer (BCO) exhibits a potent and broad spectrum fungicide activity toward plant pathogens and is now on sale in the US under the tradename FractureTM. In this work we demonstrate its antifungal activity toward human pathogens and provide some insights on its mode of action. BCO bioactivity was evaluated in eight yeast species and compared to that of amphotericin B (AMB). BCO behaved similarly to AMB in what concerns both cellular inhibition and cellular death. As a lectin, BCO binds strongly to chitin. In addition, BCO is known to possess ‘exochitinase’ and ‘endochitosanase’ activities. However, no clear disruption was visualized at the cell wall after exposure to a lethal BCO concentration, except in cell buds. Immunofluorescent and immunogold labeling clearly indicate that BCO enters the cell, and membrane destabilization was also demonstrated. The absence of haemolytic activity, its biological origin, and its extraordinary antifungal activity are the major outcomes of this work, and provide a solid background for a future application as a new antifungal therapeutic drug. Furthermore, its predictable multisite mode of action suggests a low risk of inducing resistance mechanisms, which are now a major problem with other currently available antifungal drugs. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016 2016-01-01T00:00:00Z 2017-06-05T14:49:13Z |
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/10400.5/13716 |
url |
http://hdl.handle.net/10400.5/13716 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Pinheiro AM, Carreira A, Rollo F, Fernandes R, Ferreira RB and Monteiro SA (2016) Blad-Containing Oligomer Fungicidal Activity on Human Pathogenic Yeasts. From the Outside to the Inside of the Target Cell. Front. Microbiol. 7:1803. 10.3389/fmicb.2016.01803 |
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 |
Maria Tereza dos Santos Correia (ed.) |
publisher.none.fl_str_mv |
Maria Tereza dos Santos Correia (ed.) |
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 |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799131083051106304 |