Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| 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/13061 |
Resumo: | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens. Rio de Janeiro, RJ, Brasil. |
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Duarte, Erica S. MartinsDubar, FaustineLawton, PhilippeSilva, Cristiane França daSoeiro, Maria de Nazaré C.Souza, Wanderley deBiot, ChristopheVommaro, Rossiane C.2016-03-08T17:13:35Z2016-03-08T17:13:35Z2015DUARTE, Erica S. Martins; et al. Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii. Plos One, v.10, n.5, e0125705, 23p, May 2015.1932-6203https://www.arca.fiocruz.br/handle/icict/1306110.1371/journal.pone.0125705engPublic Library of ScienceCiprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondiiinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens. Rio de Janeiro, RJ, Brasil.Université de Lille1. Unité de Glycobiologie Structurale et Fonctionnelle. UGSF.F-59650 Villeneuve d'Ascq, France / CNRS, UMR 8576, F-59650 Villeneuve d'Ascq, France.Université de Lyon. Université Claude-Bernard Lyon1. ISPB-Faculté de Pharmacie, Lyon, France.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Metrologia, Qualidade e Tecnologia—Inmetro. Rio de Janeiro, RJ, Brasil.Université de Lille1—Unité de Glycobiologie Structurale et Fonctionnelle, UGSF, F-59650 Villeneuve d'Ascq, France.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens. Rio de Janeiro, RJ, Brasil.Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite’s DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM). When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13–25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment). Light microscopy examination early (6 and 24h) post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition - with the appearance of ‘tethered’ parasites – malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results show that Cipro derivatives improved the survival of mice acutely infected with T. gondii and inhibited parasite replication early in the first cycle of infection in vitro, highlighting their therapeutic potential for the treatment of toxoplasmosis.Toxoplasma gondiiCiprofloxacin DerivativesParasite Cell DivisionMiceToxoplasmaCiprofloxacinoParasitosDivisão CelularCamundongosinfo: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/13061/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALcristiane_silva_etal_IOC_2015.PDFcristiane_silva_etal_IOC_2015.PDFapplication/pdf13614866https://www.arca.fiocruz.br/bitstream/icict/13061/2/cristiane_silva_etal_IOC_2015.PDF2c48c7ce1050d96f3698f186f0ce3a65MD52TEXTcristiane_silva_etal_IOC_2015.PDF.txtcristiane_silva_etal_IOC_2015.PDF.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii |
| title |
Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii |
| spellingShingle |
Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii Duarte, Erica S. Martins Toxoplasma gondii Ciprofloxacin Derivatives Parasite Cell Division Mice Toxoplasma Ciprofloxacino Parasitos Divisão Celular Camundongos |
| title_short |
Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii |
| title_full |
Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii |
| title_fullStr |
Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii |
| title_full_unstemmed |
Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii |
| title_sort |
Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii |
| author |
Duarte, Erica S. Martins |
| author_facet |
Duarte, Erica S. Martins Dubar, Faustine Lawton, Philippe Silva, Cristiane França da Soeiro, Maria de Nazaré C. Souza, Wanderley de Biot, Christophe Vommaro, Rossiane C. |
| author_role |
author |
| author2 |
Dubar, Faustine Lawton, Philippe Silva, Cristiane França da Soeiro, Maria de Nazaré C. Souza, Wanderley de Biot, Christophe Vommaro, Rossiane C. |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Duarte, Erica S. Martins Dubar, Faustine Lawton, Philippe Silva, Cristiane França da Soeiro, Maria de Nazaré C. Souza, Wanderley de Biot, Christophe Vommaro, Rossiane C. |
| dc.subject.en.pt_BR.fl_str_mv |
Toxoplasma gondii Ciprofloxacin Derivatives Parasite Cell Division Mice |
| topic |
Toxoplasma gondii Ciprofloxacin Derivatives Parasite Cell Division Mice Toxoplasma Ciprofloxacino Parasitos Divisão Celular Camundongos |
| dc.subject.decs.pt_BR.fl_str_mv |
Toxoplasma Ciprofloxacino Parasitos Divisão Celular Camundongos |
| description |
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens. Rio de Janeiro, RJ, Brasil. |
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2015 |
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2015 |
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2016-03-08T17:13:35Z |
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2016-03-08T17:13:35Z |
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DUARTE, Erica S. Martins; et al. Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii. Plos One, v.10, n.5, e0125705, 23p, May 2015. |
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https://www.arca.fiocruz.br/handle/icict/13061 |
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1932-6203 |
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10.1371/journal.pone.0125705 |
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DUARTE, Erica S. Martins; et al. Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii. Plos One, v.10, n.5, e0125705, 23p, May 2015. 1932-6203 10.1371/journal.pone.0125705 |
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