Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi

Detalhes bibliográficos
Autor(a) principal: Pinheiro, Ana M.
Data de Publicação: 2017
Outros Autores: Carreira, Alexandra, Prescott, Thomas A.K., Ferreira, Ricardo Boavida, Monteiro, Sara A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.5/13980
Resumo: Original Research
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spelling Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungiblad-containing oligomerantifungalmetal chelationmetal homeostasismultitarget mode of actiontoxicologyOriginal ResearchThe lack of antifungal drugs with novel modes of action reaching the clinic is a serious concern. Recently a novel antifungal protein referred to as Blad-containing oligomer (BCO) has received regulatory approval as an agricultural antifungal agent. Interestingly its spectrum of antifungal activity includes human pathogens such as Candida albicans, however, its mode of action has yet to be elucidated. Here we demonstrate that BCO exerts its antifungal activity through inhibition of metal ion homeostasis which results in apoptotic cell death in C. albicans. HIP HOP profiling in Saccharomyces cerevisiae using a panel of signature strains that are characteristic for common modes of action identified hypersensitivity in yeast lacking the iron-dependent transcription factor Aft1 suggesting restricted iron uptake as a mode of action. Furthermore, global transcriptome profiling in C. albicans also identified disruption of metal ion homeostasis as a potential mode of action. Experiments were carried out to assess the effect of divalent metal ions on the antifungal activity of BCO revealing that BCO activity is antagonized by metal ions such as Mn2C, Zn2C, and Fe2C. The transcriptome profile also implicated sterol synthesis as a possible secondary mode of action which was subsequently confirmed in sterol synthesis assays in C. albicans. Animal models for toxicity showed that BCO is generally well tolerated and presents a promising safety profile as a topical applied agent. Given its potent broad spectrum antifungal activity and novel multitarget mode of action, we propose BCO as a promising new antifungal agent for the topical treatment of fungal infectionsMiguel Cacho Teixeira (ed.)Repositório da Universidade de LisboaPinheiro, Ana M.Carreira, AlexandraPrescott, Thomas A.K.Ferreira, Ricardo BoavidaMonteiro, Sara A.2017-08-02T13:18:23Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.5/13980engPinheiro AM, Carreira A, Prescott TAK, Ferreira RB and Monteiro SA (2017) Bridging the Gap to Non-toxic Fungal Control: Lupinus-Derived Blad-Containing Oligomer as a Novel Candidate to Combat Human Pathogenic Fungi. Front. Microbiol. 8:118210.3389/fmicb.2017.01182info: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:RCAAP2023-03-06T14:44:03Zoai:www.repository.utl.pt:10400.5/13980Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:59:52.664023Repositório 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 Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi
title Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi
spellingShingle Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi
Pinheiro, Ana M.
blad-containing oligomer
antifungal
metal chelation
metal homeostasis
multitarget mode of action
toxicology
title_short Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi
title_full Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi
title_fullStr Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi
title_full_unstemmed Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi
title_sort Bridging the gap to non-toxic fungal control: lupinus-derived blad-containing ologomer as a novel candidate to combat human pathgenic fungi
author Pinheiro, Ana M.
author_facet Pinheiro, Ana M.
Carreira, Alexandra
Prescott, Thomas A.K.
Ferreira, Ricardo Boavida
Monteiro, Sara A.
author_role author
author2 Carreira, Alexandra
Prescott, Thomas A.K.
Ferreira, Ricardo Boavida
Monteiro, Sara A.
author2_role 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
Prescott, Thomas A.K.
Ferreira, Ricardo Boavida
Monteiro, Sara A.
dc.subject.por.fl_str_mv blad-containing oligomer
antifungal
metal chelation
metal homeostasis
multitarget mode of action
toxicology
topic blad-containing oligomer
antifungal
metal chelation
metal homeostasis
multitarget mode of action
toxicology
description Original Research
publishDate 2017
dc.date.none.fl_str_mv 2017-08-02T13:18:23Z
2017
2017-01-01T00:00:00Z
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/10400.5/13980
url http://hdl.handle.net/10400.5/13980
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Pinheiro AM, Carreira A, Prescott TAK, Ferreira RB and Monteiro SA (2017) Bridging the Gap to Non-toxic Fungal Control: Lupinus-Derived Blad-Containing Oligomer as a Novel Candidate to Combat Human Pathogenic Fungi. Front. Microbiol. 8:1182
10.3389/fmicb.2017.01182
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 Miguel Cacho Teixeira (ed.)
publisher.none.fl_str_mv Miguel Cacho Teixeira (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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