| Author | Almeida, Marcos Abreu | |
| Author | Bernardes-Engemann, Andrea Reis | |
| Author | Coelho, Rowena Alves | |
| Author | Lugones, Camila Jantoro Guzman | |
| Author | Andrade, Iara Bastos de | |
| Author | Corrêa-Junior, Dario | |
| Author | Oliveira, Simone Santiago Carvalho de | |
| Author | Santos, André Luis Souza dos | |
| Author | Frases, Susana | |
| Author | Rodrigues, Marcio Lourenço | |
| Author | Valente, Richard Hemmi | |
| Author | Zancopé-Oliveira, Rosely Maria | |
| Author | Almeida-Paes, Rodrigo | |
| Access date | 2023-04-17T19:03:32Z | |
| Available date | 2023-04-17T19:03:32Z | |
| Document date | 2023 | |
| Citation | 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. | en_US |
| ISSN | 2309-608X | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/57832 | |
| Language | por | en_US |
| Publisher | MDPI | en_US |
| Rights | open access | |
| Subject in Portuguese | Benzimidazóis | en_US |
| Title | Mebendazole inhibits Histoplasma capsulatum in vitro growth and decreases mitochondrion and cytoskeleton protein levels | en_US |
| Type | Article | |
| DOI | 10.3390/jof9030385 | |
| Abstract | 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Biofísica de Fungos. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Biofísica de Fungos. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | 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. | en_US |
| Subject | Histoplasmosis | en_US |
| Subject | Antifungal Agents | en_US |
| Subject | Benzimidazoles | en_US |
| Subject | Drug Repositioning | en_US |
| Subject | Proteomics | en_US |
| Subject in Spanish | Histoplasmosis | en_US |
| Subject in Spanish | Antifúngicos | en_US |
| Subject in Spanish | Bencimidazoles | en_US |
| Subject in Spanish | Reposicionamiento de Medicamentos | en_US |
| Subject in Spanish | Proteómica | en_US |
| Subject in French | Histoplasmose | en_US |
| Subject in French | Antifongiques | en_US |
| Subject in French | Benzimidazoles | en_US |
| Subject in French | Repositionnement des médicaments | en_US |
| Subject in French | Protéomique | en_US |
| DeCS | Histoplasmose | en_US |
| DeCS | Antifúngicos | en_US |
| DeCS | Benzimidazole | en_US |
| DeCS | Reposicionamento de Medicamentos | en_US |
| DeCS | Proteômica | en_US |
