Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells

Abstract Autophagy is a crucial and physiological process for cell survival from yeast to mammals, including protozoan parasites. Toxoplasma gondii, an intracellular parasite, typically exploits autophagic machinery of host cell; however host cell upregulates autophagy to combat the infection. Herei...

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Autores principales:	Francesca Ietta, Emanuela Maioli, Elena Daveri, Juliana Gonzaga Oliveira, Rafaela José da Silva, Roberta Romagnoli, Laura Cresti, Anna Maria Avanzati, Luana Paulesu, Bellisa de Freitas Barbosa, Angelica de Oliveira Gomes, José Roberto Mineo, Eloisa Amália Vieira Ferro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b4d5148a8754f74bcf568259faac13a
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spelling	oai:doaj.org-article:1b4d5148a8754f74bcf568259faac13a2021-12-02T11:53:07ZRottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells10.1038/s41598-017-01525-62045-2322https://doaj.org/article/1b4d5148a8754f74bcf568259faac13a2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01525-6https://doaj.org/toc/2045-2322Abstract Autophagy is a crucial and physiological process for cell survival from yeast to mammals, including protozoan parasites. Toxoplasma gondii, an intracellular parasite, typically exploits autophagic machinery of host cell; however host cell upregulates autophagy to combat the infection. Herein we tested the efficacy of Rottlerin, a natural polyphenol with autophagic promoting properties, against Toxoplasma infection on the chorioncarcinoma-derived cell line BeWo. We found that Rottlerin, at sub-toxic doses, induced morphological and biochemical alterations associated with autophagy and decreased Toxoplasma growth in infected cells. Although autophagy was synergically promoted by Toxoplasma infection in combination with Rottlerin treatment, the use of the autophagy inhibitor chloroquine revealed that Rottlerin anti-parasitic effect was largely autophagy-independent and likely mediated by the converging inhibitory effect of Rottlerin and Toxoplasma in host protein translation, mediated by mTOR inhibition and eIF2α phosphorylation. Both events, which on one hand could explain the additive effect on autophagy induction, on the other hand led to inhibition of protein synthesis, thereby depriving Toxoplasma of metabolically essential components for multiplication. We suggest that modulation of the competition between pathogen requirement and host cell defense might be an attractive, novel therapeutic approach against Toxoplasma infection and encourage the development of Rottlerin-based new therapeutic formulations.Francesca IettaEmanuela MaioliElena DaveriJuliana Gonzaga OliveiraRafaela José da SilvaRoberta RomagnoliLaura CrestiAnna Maria AvanzatiLuana PaulesuBellisa de Freitas BarbosaAngelica de Oliveira GomesJosé Roberto MineoEloisa Amália Vieira FerroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francesca Ietta Emanuela Maioli Elena Daveri Juliana Gonzaga Oliveira Rafaela José da Silva Roberta Romagnoli Laura Cresti Anna Maria Avanzati Luana Paulesu Bellisa de Freitas Barbosa Angelica de Oliveira Gomes José Roberto Mineo Eloisa Amália Vieira Ferro Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells
description	Abstract Autophagy is a crucial and physiological process for cell survival from yeast to mammals, including protozoan parasites. Toxoplasma gondii, an intracellular parasite, typically exploits autophagic machinery of host cell; however host cell upregulates autophagy to combat the infection. Herein we tested the efficacy of Rottlerin, a natural polyphenol with autophagic promoting properties, against Toxoplasma infection on the chorioncarcinoma-derived cell line BeWo. We found that Rottlerin, at sub-toxic doses, induced morphological and biochemical alterations associated with autophagy and decreased Toxoplasma growth in infected cells. Although autophagy was synergically promoted by Toxoplasma infection in combination with Rottlerin treatment, the use of the autophagy inhibitor chloroquine revealed that Rottlerin anti-parasitic effect was largely autophagy-independent and likely mediated by the converging inhibitory effect of Rottlerin and Toxoplasma in host protein translation, mediated by mTOR inhibition and eIF2α phosphorylation. Both events, which on one hand could explain the additive effect on autophagy induction, on the other hand led to inhibition of protein synthesis, thereby depriving Toxoplasma of metabolically essential components for multiplication. We suggest that modulation of the competition between pathogen requirement and host cell defense might be an attractive, novel therapeutic approach against Toxoplasma infection and encourage the development of Rottlerin-based new therapeutic formulations.
format	article
author	Francesca Ietta Emanuela Maioli Elena Daveri Juliana Gonzaga Oliveira Rafaela José da Silva Roberta Romagnoli Laura Cresti Anna Maria Avanzati Luana Paulesu Bellisa de Freitas Barbosa Angelica de Oliveira Gomes José Roberto Mineo Eloisa Amália Vieira Ferro
author_facet	Francesca Ietta Emanuela Maioli Elena Daveri Juliana Gonzaga Oliveira Rafaela José da Silva Roberta Romagnoli Laura Cresti Anna Maria Avanzati Luana Paulesu Bellisa de Freitas Barbosa Angelica de Oliveira Gomes José Roberto Mineo Eloisa Amália Vieira Ferro
author_sort	Francesca Ietta
title	Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells
title_short	Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells
title_full	Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells
title_fullStr	Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells
title_full_unstemmed	Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells
title_sort	rottlerin-mediated inhibition of toxoplasma gondii growth in bewo trophoblast-like cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1b4d5148a8754f74bcf568259faac13a
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Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells

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