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. 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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ietta F,Maioli E,Daveri E,Gonzaga Oliveira J,da Silva RJ,Romagnoli R,Cresti L,Maria Avanzati A,Paulesu L,Barbosa BF,Gomes AO,Roberto Mineo J,Ferro EAV

doi

10.1038/s41598-017-01525-6

subject

Has Abstract

pub_date

2017-04-28 00:00:00

pages

1279

issue

1

issn

2045-2322

pii

10.1038/s41598-017-01525-6

journal_volume

7

pub_type

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