Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery

Detalhes bibliográficos
Autor(a) principal: Costa, DM
Data de Publicação: 2019
Outros Autores: Cecílio, P, Santarém, N, Cordeiro-da-Silva, A, Tavares, J
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/138983
Resumo: Leishmaniasis is an important vector-borne neglected tropical disease caused by Leishmania parasites. Current anti-Leishmania chemotherapy is unsatisfactory, justifying the continued search for alternative treatment options. Herein, we demonstrate that luciferase-expressing Leishmania infantum axenic amastigotes, unlike promastigotes, are highly infectious to BALB/c mice and thus generate a robust bioluminescent signal in target organs, such as the liver and the spleen, as early as two weeks after infection. Treatment with the reference drugs amphotericin B and miltefosine was effective at reducing parasite burdens. This model allows the assessment of treatment efficacy using whole-mouse bioluminescence imaging without the need to wait several weeks for spleen infections to be detectable by this non-invasive method. In conclusion, we propose the use of this model in an initial approach to evaluate the treatment efficacy of promising chemical entities without having to sacrifice large numbers of animals or to wait several days for a readout.
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spelling Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discoveryLeishmaniasis is an important vector-borne neglected tropical disease caused by Leishmania parasites. Current anti-Leishmania chemotherapy is unsatisfactory, justifying the continued search for alternative treatment options. Herein, we demonstrate that luciferase-expressing Leishmania infantum axenic amastigotes, unlike promastigotes, are highly infectious to BALB/c mice and thus generate a robust bioluminescent signal in target organs, such as the liver and the spleen, as early as two weeks after infection. Treatment with the reference drugs amphotericin B and miltefosine was effective at reducing parasite burdens. This model allows the assessment of treatment efficacy using whole-mouse bioluminescence imaging without the need to wait several weeks for spleen infections to be detectable by this non-invasive method. In conclusion, we propose the use of this model in an initial approach to evaluate the treatment efficacy of promising chemical entities without having to sacrifice large numbers of animals or to wait several days for a readout.Nature Publishing Group20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/138983eng2045-232210.1038/s41598-019-55474-3Costa, DMCecílio, PSantarém, NCordeiro-da-Silva, ATavares, Jinfo: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:RCAAP2024-09-27T07:54:33Zoai:repositorio-aberto.up.pt:10216/138983Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-09-27T07:54:33Repositório 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 Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
title Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
spellingShingle Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
Costa, DM
title_short Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
title_full Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
title_fullStr Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
title_full_unstemmed Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
title_sort Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
author Costa, DM
author_facet Costa, DM
Cecílio, P
Santarém, N
Cordeiro-da-Silva, A
Tavares, J
author_role author
author2 Cecílio, P
Santarém, N
Cordeiro-da-Silva, A
Tavares, J
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Costa, DM
Cecílio, P
Santarém, N
Cordeiro-da-Silva, A
Tavares, J
description Leishmaniasis is an important vector-borne neglected tropical disease caused by Leishmania parasites. Current anti-Leishmania chemotherapy is unsatisfactory, justifying the continued search for alternative treatment options. Herein, we demonstrate that luciferase-expressing Leishmania infantum axenic amastigotes, unlike promastigotes, are highly infectious to BALB/c mice and thus generate a robust bioluminescent signal in target organs, such as the liver and the spleen, as early as two weeks after infection. Treatment with the reference drugs amphotericin B and miltefosine was effective at reducing parasite burdens. This model allows the assessment of treatment efficacy using whole-mouse bioluminescence imaging without the need to wait several weeks for spleen infections to be detectable by this non-invasive method. In conclusion, we propose the use of this model in an initial approach to evaluate the treatment efficacy of promising chemical entities without having to sacrifice large numbers of animals or to wait several days for a readout.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
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 https://hdl.handle.net/10216/138983
url https://hdl.handle.net/10216/138983
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2045-2322
10.1038/s41598-019-55474-3
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dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 mluisa.alvim@gmail.com
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