17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death

Detalhes bibliográficos
Autor(a) principal: Petersen, Antonio Luis de O. A.
Data de Publicação: 2021
Outros Autores: Cull, Benjamin, Dias, Beatriz R. S., Palma, Luana C., Luz, Yasmin da S., Menezes, Juliana Perrone Bezerra de, Mottram, Jeremy C., Veras, Patrícia Sampaio Tavares
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/47739
Resumo: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001
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spelling Petersen, Antonio Luis de O. A.Cull, BenjaminDias, Beatriz R. S.Palma, Luana C.Luz, Yasmin da S.Menezes, Juliana Perrone Bezerra deMottram, Jeremy C.Veras, Patrícia Sampaio Tavares2021-06-17T12:38:00Z2021-06-17T12:38:00Z2021PETERSEN, Antonio Luis de O. A. et al. 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death. Microorganisms, v. 9, n. 5, p. 1-15, 19 Mar. 2021.2076-2607https://www.arca.fiocruz.br/handle/icict/4773910.3390/microorganisms9051089Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001Fundação de Amparo à Pesquisa do Estado da BahiaCNPq (P.S.T.V.—Universal 422867/2016-0 http://www.cnpq.br, (accessed on 30 August 2016)Medical Research Council (MR/K019384/1)CNPq for productivity in research (307832/2015-5)Medical Research Council studentshipFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.University of Glasgow. College of Medical, Veterinary & Life Sciences. Institute of Infection, Immunity & Inflammation. Wellcome Centre for Integrative Parasitology. Glasgow, UK.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Programa de Pós-Graduação em Patologia Humana e Experimental. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.University of Glasgow. College of Medical, Veterinary & Life Sciences. Institute of Infection, Immunity & Inflammation. Wellcome Centre for Integrative Parasitology. Glasgow, UK. / University of York. Department of Biology. York Biomedical Research Institute. York, UK.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil. / Conselho Nacional de Desenvolvimento Científico e Tecnológico. Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Brasília, DF, Brasil.The heat shock protein 90 (Hsp90) is thought to be an excellent drug target against parasitic diseases. The leishmanicidal effect of an Hsp90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), was previously demonstrated in both in vitro and in vivo models of cutaneous leishmaniasis. Parasite death was shown to occur in association with severe ultrastructural alterations in Leishmania, suggestive of autophagic activation. We hypothesized that 17-AAG treatment results in the abnormal activation of the autophagic pathway, leading to parasite death. To elucidate this process, experiments were performed using transgenic parasites with GFP-ATG8-labelled autophagosomes. Mutant parasites treated with 17-AAG exhibited autophagosomes that did not entrap cargo, such as glycosomes, or fuse with lysosomes. ATG5-knockout (∆atg5) parasites, which are incapable of forming autophagosomes, demonstrated lower sensitivity to 17-AAG-induced cell death when compared to wild-type (WT) Leishmania, further supporting the role of autophagy in 17-AAG-induced cell death. In addition, Hsp90 inhibition resulted in greater accumulation of ubiquitylated proteins in both WT- and ∆atg5-treated parasites compared to controls, in the absence of proteasome overload. In conjunction with previously described ultrastructural alterations, herein we present evidence that treatment with 17-AAG causes abnormal activation of the autophagic pathway, resulting in the formation of immature autophagosomes and, consequently, incidental parasite death.engMDPIHsp90LeishmanioseQuimioterapiaInibidores das Hsp90AutofagiaUbiquitinaHsp90LeishmaniasisChemotherapyHsp90 inhibitorsAutophagyUbiquitin17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite deathinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/47739/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALPetersen, Antonio Luis de O.A 17-AAG induced....pdfPetersen, Antonio Luis de O.A 17-AAG induced....pdfapplication/pdf3668290https://www.arca.fiocruz.br/bitstream/icict/47739/2/Petersen%2c%20Antonio%20Luis%20de%20O.A%2017-AAG%20induced....pdfb5d44756f95bb19e7f848a349c3b7ee0MD52TEXTPetersen, Antonio Luis de O.A 17-AAG induced....pdf.txtPetersen, Antonio Luis de O.A 17-AAG induced....pdf.txtExtracted texttext/plain49688https://www.arca.fiocruz.br/bitstream/icict/47739/3/Petersen%2c%20Antonio%20Luis%20de%20O.A%2017-AAG%20induced....pdf.txt9d2211ad35e23f1e786cfe5135f58d6dMD53icict/477392023-03-15 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dc.title.en.fl_str_mv 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
title 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
spellingShingle 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
Petersen, Antonio Luis de O. A.
Hsp90
Leishmaniose
Quimioterapia
Inibidores das Hsp90
Autofagia
Ubiquitina
Hsp90
Leishmaniasis
Chemotherapy
Hsp90 inhibitors
Autophagy
Ubiquitin
title_short 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
title_full 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
title_fullStr 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
title_full_unstemmed 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
title_sort 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
author Petersen, Antonio Luis de O. A.
author_facet Petersen, Antonio Luis de O. A.
Cull, Benjamin
Dias, Beatriz R. S.
Palma, Luana C.
Luz, Yasmin da S.
Menezes, Juliana Perrone Bezerra de
Mottram, Jeremy C.
Veras, Patrícia Sampaio Tavares
author_role author
author2 Cull, Benjamin
Dias, Beatriz R. S.
Palma, Luana C.
Luz, Yasmin da S.
Menezes, Juliana Perrone Bezerra de
Mottram, Jeremy C.
Veras, Patrícia Sampaio Tavares
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Petersen, Antonio Luis de O. A.
Cull, Benjamin
Dias, Beatriz R. S.
Palma, Luana C.
Luz, Yasmin da S.
Menezes, Juliana Perrone Bezerra de
Mottram, Jeremy C.
Veras, Patrícia Sampaio Tavares
dc.subject.other.pt_BR.fl_str_mv Hsp90
Leishmaniose
Quimioterapia
Inibidores das Hsp90
Autofagia
Ubiquitina
topic Hsp90
Leishmaniose
Quimioterapia
Inibidores das Hsp90
Autofagia
Ubiquitina
Hsp90
Leishmaniasis
Chemotherapy
Hsp90 inhibitors
Autophagy
Ubiquitin
dc.subject.en.en.fl_str_mv Hsp90
Leishmaniasis
Chemotherapy
Hsp90 inhibitors
Autophagy
Ubiquitin
description Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-06-17T12:38:00Z
dc.date.available.fl_str_mv 2021-06-17T12:38:00Z
dc.date.issued.fl_str_mv 2021
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.citation.fl_str_mv PETERSEN, Antonio Luis de O. A. et al. 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death. Microorganisms, v. 9, n. 5, p. 1-15, 19 Mar. 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/47739
dc.identifier.issn.pt_BR.fl_str_mv 2076-2607
dc.identifier.doi.pt_BR.fl_str_mv 10.3390/microorganisms9051089
identifier_str_mv PETERSEN, Antonio Luis de O. A. et al. 17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death. Microorganisms, v. 9, n. 5, p. 1-15, 19 Mar. 2021.
2076-2607
10.3390/microorganisms9051089
url https://www.arca.fiocruz.br/handle/icict/47739
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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