Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
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/1822/66984 |
Resumo: | Candida albicans is one of the most impactful fungal pathogens and the most common cause of invasive candidiasis, which is associated with very high mortality rates. With the rise in the frequency of multidrug-resistant clinical isolates, the identification of new drug targets and new drugs is crucial in overcoming the increase in therapeutic failure. In this study, the first validated genome-scale metabolic model for Candida albicans, iRV781, is presented. The model consists of 1221 reactions, 926 metabolites, 781 genes, and four compartments. This model was reconstructed using the open-source software tool merlin 4.0.2. It is provided in the well-established systems biology markup language (SBML) format, thus, being usable in most metabolic engineering platforms, such as OptFlux or COBRA. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources when compared to experimental data. Finally, this genome-scale metabolic reconstruction was tested as a platform for the identification of drug targets, through the comparison between known drug targets and the prediction of gene essentiality in conditions mimicking the human host. Altogether, this model provides a promising platform for global elucidation of the metabolic potential of C. albicans, possibly guiding the identification of new drug targets to tackle human candidiasis. |
id |
RCAP_1e61d0de5aa4264147bd6047aeefe462 |
---|---|
oai_identifier_str |
oai:repositorium.sdum.uminho.pt:1822/66984 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target predictionCandida albicansGlobal stoichiometric modelDrug targetsMetabolic reconstructionGene essentialityCiências Médicas::Biotecnologia MédicaScience & TechnologyCandida albicans is one of the most impactful fungal pathogens and the most common cause of invasive candidiasis, which is associated with very high mortality rates. With the rise in the frequency of multidrug-resistant clinical isolates, the identification of new drug targets and new drugs is crucial in overcoming the increase in therapeutic failure. In this study, the first validated genome-scale metabolic model for Candida albicans, iRV781, is presented. The model consists of 1221 reactions, 926 metabolites, 781 genes, and four compartments. This model was reconstructed using the open-source software tool merlin 4.0.2. It is provided in the well-established systems biology markup language (SBML) format, thus, being usable in most metabolic engineering platforms, such as OptFlux or COBRA. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources when compared to experimental data. Finally, this genome-scale metabolic reconstruction was tested as a platform for the identification of drug targets, through the comparison between known drug targets and the prediction of gene essentiality in conditions mimicking the human host. Altogether, this model provides a promising platform for global elucidation of the metabolic potential of C. albicans, possibly guiding the identification of new drug targets to tackle human candidiasis.“Fundação para a Ciência e a Tecnologia” (FCT) [Contract PTDC /BII-BIO/28216/2017] and by Programa Operacional Regional de Lisboa 2020 [LISBOA-01-0145-FEDER-022231], through the Biodata.pt Research Infrastructure. Funding received by iBB-Institute for Bioengineering and Biosciences from FCT [Contract UIDB/04565/2020]info:eu-repo/semantics/publishedVersionMDPIUniversidade do MinhoViana, RomeuDias, OscarLagoa, Davide Rafael SantosGalocha, MónicaRocha, IsabelTeixeira, Miguel Cacho2020-09-112020-09-11T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/66984engViana, Romeu; Dias, Oscar; Lagoa, D.; Galocha, Mónica; Rocha, Isabel; Teixeira, Miguel Cacho, Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction. Journal of Fungi, 6(3), 171, 20202309-608X10.3390/jof6030171https://www.mdpi.com/2309-608X/6/3/171info: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:RCAAP2023-07-21T12:34:12Zoai:repositorium.sdum.uminho.pt:1822/66984Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:29:49.774838Repositório 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 |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction |
title |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction |
spellingShingle |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction Viana, Romeu Candida albicans Global stoichiometric model Drug targets Metabolic reconstruction Gene essentiality Ciências Médicas::Biotecnologia Médica Science & Technology |
title_short |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction |
title_full |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction |
title_fullStr |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction |
title_full_unstemmed |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction |
title_sort |
Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction |
author |
Viana, Romeu |
author_facet |
Viana, Romeu Dias, Oscar Lagoa, Davide Rafael Santos Galocha, Mónica Rocha, Isabel Teixeira, Miguel Cacho |
author_role |
author |
author2 |
Dias, Oscar Lagoa, Davide Rafael Santos Galocha, Mónica Rocha, Isabel Teixeira, Miguel Cacho |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Viana, Romeu Dias, Oscar Lagoa, Davide Rafael Santos Galocha, Mónica Rocha, Isabel Teixeira, Miguel Cacho |
dc.subject.por.fl_str_mv |
Candida albicans Global stoichiometric model Drug targets Metabolic reconstruction Gene essentiality Ciências Médicas::Biotecnologia Médica Science & Technology |
topic |
Candida albicans Global stoichiometric model Drug targets Metabolic reconstruction Gene essentiality Ciências Médicas::Biotecnologia Médica Science & Technology |
description |
Candida albicans is one of the most impactful fungal pathogens and the most common cause of invasive candidiasis, which is associated with very high mortality rates. With the rise in the frequency of multidrug-resistant clinical isolates, the identification of new drug targets and new drugs is crucial in overcoming the increase in therapeutic failure. In this study, the first validated genome-scale metabolic model for Candida albicans, iRV781, is presented. The model consists of 1221 reactions, 926 metabolites, 781 genes, and four compartments. This model was reconstructed using the open-source software tool merlin 4.0.2. It is provided in the well-established systems biology markup language (SBML) format, thus, being usable in most metabolic engineering platforms, such as OptFlux or COBRA. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources when compared to experimental data. Finally, this genome-scale metabolic reconstruction was tested as a platform for the identification of drug targets, through the comparison between known drug targets and the prediction of gene essentiality in conditions mimicking the human host. Altogether, this model provides a promising platform for global elucidation of the metabolic potential of C. albicans, possibly guiding the identification of new drug targets to tackle human candidiasis. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-09-11 2020-09-11T00:00:00Z |
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/1822/66984 |
url |
http://hdl.handle.net/1822/66984 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Viana, Romeu; Dias, Oscar; Lagoa, D.; Galocha, Mónica; Rocha, Isabel; Teixeira, Miguel Cacho, Genome-scale metabolic model of the human pathogen Candida albicans: a promising platform for drug target prediction. Journal of Fungi, 6(3), 171, 2020 2309-608X 10.3390/jof6030171 https://www.mdpi.com/2309-608X/6/3/171 |
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 |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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 |
|
_version_ |
1799132800222232576 |