17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , |
| 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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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 |
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 |
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2021 |
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2021-06-17T12:38:00Z |
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2021-06-17T12:38:00Z |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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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. |
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https://www.arca.fiocruz.br/handle/icict/47739 |
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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 |
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