Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection
Autor(a) principal: | |
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Data de Publicação: | 2010 |
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/1822/29532 |
Resumo: | The incidence of Candida albicans infections and the relapse episodes after antifungal treatment have increased in recent decades. Recurrences are mainly due to the persistence of the original infecting strain that may present genetic and genomic rearrangements during interaction with the host, reflecting strain adaptation. In this study, four isolates recovered from a patient during recurrent candidemia episodes were genotyped by microsatellite length polymorphism (MLP) and by multilocus sequence typing (MLST) and found to be genetic variants of the same strain. Using experimental mouse infections, a progressive reduction in the virulence of the four isolates was observed, with the first two isolates more virulent than the third and fourth. Additionally, in the mouse model, the first isolate resisted host control more efficiently, resulting in higher kidney fungal burdens and necrosis as compared to the third isolate. The resolution of inflammation was delayed in mice challenged with the first isolate and the message for IFN-gamma and TNF-alpha in the spleen was lower within the first few hours post-infection. Original and recurrent isolates also displayed different phenotypes regarding activity of secreted enzymes and response to stress agents. Overall, the comparative analysis indicated that the virulence decrease of these isolates was related to a lower ability to resist to the host anticandida effector mechanisms. We showed for the first time that C. albicans genetic variants of the same strain, sequentially isolated from an immunocompromised patient, underwent adaptations in the human host that resulted in virulence attenuation when tested in mice. |
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Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infectionScience & TechnologyThe incidence of Candida albicans infections and the relapse episodes after antifungal treatment have increased in recent decades. Recurrences are mainly due to the persistence of the original infecting strain that may present genetic and genomic rearrangements during interaction with the host, reflecting strain adaptation. In this study, four isolates recovered from a patient during recurrent candidemia episodes were genotyped by microsatellite length polymorphism (MLP) and by multilocus sequence typing (MLST) and found to be genetic variants of the same strain. Using experimental mouse infections, a progressive reduction in the virulence of the four isolates was observed, with the first two isolates more virulent than the third and fourth. Additionally, in the mouse model, the first isolate resisted host control more efficiently, resulting in higher kidney fungal burdens and necrosis as compared to the third isolate. The resolution of inflammation was delayed in mice challenged with the first isolate and the message for IFN-gamma and TNF-alpha in the spleen was lower within the first few hours post-infection. Original and recurrent isolates also displayed different phenotypes regarding activity of secreted enzymes and response to stress agents. Overall, the comparative analysis indicated that the virulence decrease of these isolates was related to a lower ability to resist to the host anticandida effector mechanisms. We showed for the first time that C. albicans genetic variants of the same strain, sequentially isolated from an immunocompromised patient, underwent adaptations in the human host that resulted in virulence attenuation when tested in mice.This work was supported by Fundac¸a˜o para a Cieˆncia e Tecnologia (FCT) through the project POCI/SAU-IMI/58014/2004 and by a Grant from the Health Services of Fundac¸a˜o Calouste Gulbenkian. Julio Chavez-Galarza was supported by an ALbAN scholarship (Nu E06M103915PE), and Alexandra Correia by SFRH/BD/ 31354/2006 fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.PLOSUniversidade do MinhoSampaio, PaulaSantos, MarleneCorreia, AlexandraAmaral, Fábio E.Chávez Galarza, Júlio CésarOliveira, Sofia Costa deCastro, António G.Pedrosa, JorgePais, Célia2010-04-132010-04-13T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/29532eng1932-620310.1371/journal.pone.001015520405013http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010155info: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:RCAAP2023-07-21T12:40:44Zoai:repositorium.sdum.uminho.pt:1822/29532Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:37:35.053094Repositório 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 |
Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection |
title |
Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection |
spellingShingle |
Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection Sampaio, Paula Science & Technology |
title_short |
Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection |
title_full |
Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection |
title_fullStr |
Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection |
title_full_unstemmed |
Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection |
title_sort |
Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection |
author |
Sampaio, Paula |
author_facet |
Sampaio, Paula Santos, Marlene Correia, Alexandra Amaral, Fábio E. Chávez Galarza, Júlio César Oliveira, Sofia Costa de Castro, António G. Pedrosa, Jorge Pais, Célia |
author_role |
author |
author2 |
Santos, Marlene Correia, Alexandra Amaral, Fábio E. Chávez Galarza, Júlio César Oliveira, Sofia Costa de Castro, António G. Pedrosa, Jorge Pais, Célia |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Sampaio, Paula Santos, Marlene Correia, Alexandra Amaral, Fábio E. Chávez Galarza, Júlio César Oliveira, Sofia Costa de Castro, António G. Pedrosa, Jorge Pais, Célia |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
The incidence of Candida albicans infections and the relapse episodes after antifungal treatment have increased in recent decades. Recurrences are mainly due to the persistence of the original infecting strain that may present genetic and genomic rearrangements during interaction with the host, reflecting strain adaptation. In this study, four isolates recovered from a patient during recurrent candidemia episodes were genotyped by microsatellite length polymorphism (MLP) and by multilocus sequence typing (MLST) and found to be genetic variants of the same strain. Using experimental mouse infections, a progressive reduction in the virulence of the four isolates was observed, with the first two isolates more virulent than the third and fourth. Additionally, in the mouse model, the first isolate resisted host control more efficiently, resulting in higher kidney fungal burdens and necrosis as compared to the third isolate. The resolution of inflammation was delayed in mice challenged with the first isolate and the message for IFN-gamma and TNF-alpha in the spleen was lower within the first few hours post-infection. Original and recurrent isolates also displayed different phenotypes regarding activity of secreted enzymes and response to stress agents. Overall, the comparative analysis indicated that the virulence decrease of these isolates was related to a lower ability to resist to the host anticandida effector mechanisms. We showed for the first time that C. albicans genetic variants of the same strain, sequentially isolated from an immunocompromised patient, underwent adaptations in the human host that resulted in virulence attenuation when tested in mice. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-04-13 2010-04-13T00:00:00Z |
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/1822/29532 |
url |
http://hdl.handle.net/1822/29532 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1932-6203 10.1371/journal.pone.0010155 20405013 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010155 |
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 |
PLOS |
publisher.none.fl_str_mv |
PLOS |
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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1799132909445054464 |