Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/57832 |
Resumo: | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. |
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Almeida, Marcos AbreuBernardes-Engemann, Andrea ReisCoelho, Rowena AlvesLugones, Camila Jantoro GuzmanAndrade, Iara Bastos deCorrêa-Junior, DarioOliveira, Simone Santiago Carvalho deSantos, André Luis Souza dosFrases, SusanaRodrigues, Marcio LourençoValente, Richard HemmiZancopé-Oliveira, Rosely MariaAlmeida-Paes, Rodrigo2023-04-17T19:03:32Z2023-04-17T19:03:32Z2023ALMEIDA, Marcos Abreu et al. Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels. Journal of Fungi, v. 9, n. 385, p. 1-18, 2023.2309-608Xhttps://www.arca.fiocruz.br/handle/icict/5783210.3390/jof9030385porMDPIBenzimidazóisHistoplasmosisAntifungal AgentsBenzimidazolesDrug RepositioningProteomicsHistoplasmosisAntifúngicosBencimidazolesReposicionamiento de MedicamentosProteómicaHistoplasmoseAntifongiquesBenzimidazolesRepositionnement des médicamentsProtéomiqueHistoplasmoseAntifúngicosBenzimidazoleReposicionamento de MedicamentosProteômicaMebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levelsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Biofísica de Fungos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Biofísica de Fungos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Rio de Janeiro, RJ, Brasil. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Rio de Janeiro, RJ, Brasil. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes / Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. Rede Micologia RJ, Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Biofísica de Fungos. Rio de Janeiro, RJ, Brasil / Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. Rede Micologia RJ. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil / Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. Rede Micologia RJ. Rio de Janeiro, RJ, Brasil.Histoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if treatment is unsuccessful. Itraconazole and amphotericin B are used to treat histoplasmosis; however, both antifungals have potentially severe pharmacokinetic drug interactions and toxicity. The present study determined the minimal inhibitory and fungicidal concentrations of mebendazole, a drug present in the NIH Clinical Collection, to establish whether it has fungicidal or fungistatic activity against Histoplasma capsulatum. Protein extracts from H. capsulatum yeasts, treated or not with mebendazole, were analyzed by proteomics to understand the metabolic changes driven by this benzimidazole. Mebendazole inhibited the growth of 10 H. capsulatum strains, presenting minimal inhibitory concentrations ranging from 5.0 to 0.08 µM. Proteomics revealed 30 and 18 proteins exclusively detected in untreated and mebendazole-treated H. capsulatum yeast cells, respectively. Proteins related to the tricarboxylic acid cycle, cytoskeleton, and ribosomes were highly abundant in untreated cells. Proteins related to the nitrogen, sulfur, and pyrimidine metabolisms were enriched in mebendazole-treated cells. Furthermore, mebendazole was able to inhibit the oxidative metabolism, disrupt the cytoskeleton, and decrease ribosomal proteins in H. capsulatum. These results suggest mebendazole as a drug to be repurposed for histoplasmosis treatment.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/57832/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALjof-09-00385-v2OK.pdfjof-09-00385-v2OK.pdfapplication/pdf3883575https://www.arca.fiocruz.br/bitstream/icict/57832/2/jof-09-00385-v2OK.pdfc366b1e43d1274a76ea9c808168287bdMD52icict/578322023-10-03 15:50:51.542oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-10-03T18:50:51Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.en_US.fl_str_mv |
Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels |
| title |
Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels |
| spellingShingle |
Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels Almeida, Marcos Abreu Benzimidazóis Histoplasmosis Antifungal Agents Benzimidazoles Drug Repositioning Proteomics Histoplasmosis Antifúngicos Bencimidazoles Reposicionamiento de Medicamentos Proteómica Histoplasmose Antifongiques Benzimidazoles Repositionnement des médicaments Protéomique Histoplasmose Antifúngicos Benzimidazole Reposicionamento de Medicamentos Proteômica |
| title_short |
Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels |
| title_full |
Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels |
| title_fullStr |
Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels |
| title_full_unstemmed |
Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels |
| title_sort |
Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels |
| author |
Almeida, Marcos Abreu |
| author_facet |
Almeida, Marcos Abreu Bernardes-Engemann, Andrea Reis Coelho, Rowena Alves Lugones, Camila Jantoro Guzman Andrade, Iara Bastos de Corrêa-Junior, Dario Oliveira, Simone Santiago Carvalho de Santos, André Luis Souza dos Frases, Susana Rodrigues, Marcio Lourenço Valente, Richard Hemmi Zancopé-Oliveira, Rosely Maria Almeida-Paes, Rodrigo |
| author_role |
author |
| author2 |
Bernardes-Engemann, Andrea Reis Coelho, Rowena Alves Lugones, Camila Jantoro Guzman Andrade, Iara Bastos de Corrêa-Junior, Dario Oliveira, Simone Santiago Carvalho de Santos, André Luis Souza dos Frases, Susana Rodrigues, Marcio Lourenço Valente, Richard Hemmi Zancopé-Oliveira, Rosely Maria Almeida-Paes, Rodrigo |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Almeida, Marcos Abreu Bernardes-Engemann, Andrea Reis Coelho, Rowena Alves Lugones, Camila Jantoro Guzman Andrade, Iara Bastos de Corrêa-Junior, Dario Oliveira, Simone Santiago Carvalho de Santos, André Luis Souza dos Frases, Susana Rodrigues, Marcio Lourenço Valente, Richard Hemmi Zancopé-Oliveira, Rosely Maria Almeida-Paes, Rodrigo |
| dc.subject.other.en_US.fl_str_mv |
Benzimidazóis |
| topic |
Benzimidazóis Histoplasmosis Antifungal Agents Benzimidazoles Drug Repositioning Proteomics Histoplasmosis Antifúngicos Bencimidazoles Reposicionamiento de Medicamentos Proteómica Histoplasmose Antifongiques Benzimidazoles Repositionnement des médicaments Protéomique Histoplasmose Antifúngicos Benzimidazole Reposicionamento de Medicamentos Proteômica |
| dc.subject.en.en_US.fl_str_mv |
Histoplasmosis Antifungal Agents Benzimidazoles Drug Repositioning Proteomics |
| dc.subject.es.en_US.fl_str_mv |
Histoplasmosis Antifúngicos Bencimidazoles Reposicionamiento de Medicamentos Proteómica |
| dc.subject.fr.en_US.fl_str_mv |
Histoplasmose Antifongiques Benzimidazoles Repositionnement des médicaments Protéomique |
| dc.subject.decs.en_US.fl_str_mv |
Histoplasmose Antifúngicos Benzimidazole Reposicionamento de Medicamentos Proteômica |
| description |
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. |
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2023 |
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2023-04-17T19:03:32Z |
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2023-04-17T19:03:32Z |
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2023 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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ALMEIDA, Marcos Abreu et al. Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels. Journal of Fungi, v. 9, n. 385, p. 1-18, 2023. |
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https://www.arca.fiocruz.br/handle/icict/57832 |
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2309-608X |
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10.3390/jof9030385 |
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ALMEIDA, Marcos Abreu et al. Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels. Journal of Fungi, v. 9, n. 385, p. 1-18, 2023. 2309-608X 10.3390/jof9030385 |
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