Dataset Information

ERM Proteins Play Distinct Roles in Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi.

ABSTRACT: The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas' disease. In mammalian hosts, T. cruzi alternates between trypomastigote and amastigote forms. Additionally, trypomastigotes can differentiate into amastigotes in the extracellular environment generating infective extracellular amastigotes (EAs). Ezrin-radixin-moesin (ERM) are key proteins linking plasma membrane to actin filaments, the major host cell component responsible for EA internalization. Our results revealed that depletion of host ezrin and radixin but not moesin inhibited EAs invasion in HeLa cells. ERM are recruited and colocalize with F-actin at EA invasion sites as shown by confocal microscopy. Invasion assays performed with cells overexpressing ERM showed increased EAs invasion in ezrin and radixin but not moesin overexpressing cells. Finally, time-lapse experiments have shown altered actin dynamics leading to delayed EA internalization in ezrin and radixin depleted cells when compared to control or moesin depleted cells. Altogether, these findings show distinct roles of ERM during EAs invasion, possibly regulating F-actin dynamics and plasma membrane interplay.

SUBMITTER: Ferreira ER

PROVIDER: S-EPMC5702390 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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ERM Proteins Play Distinct Roles in Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi.

Ferreira Éden R ÉR Bonfim-Melo Alexis A Cordero Esteban M EM Mortara Renato A RA

Frontiers in microbiology 20171121

The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas' disease. In mammalian hosts, T. cruzi alternates between trypomastigote and amastigote forms. Additionally, trypomastigotes can differentiate into amastigotes in the extracellular environment generating infective extracellular amastigotes (EAs). Ezrin-radixin-moesin (ERM) are key proteins linking plasma membrane to actin filaments, the major host cell component responsible for EA internalization. Our results ...[more]

PMID: 29209287

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Project description:Obligate intracellular pathogens satisfy their nutrient requirements by coupling to host metabolic processes, often modulating these pathways to facilitate access to key metabolites. Such metabolic dependencies represent potential targets for pathogen control, but remain largely uncharacterized for the intracellular protozoan parasite and causative agent of Chagas disease, Trypanosoma cruzi. Perturbations in host central carbon and energy metabolism have been reported in mammalian T. cruzi infection, with no information regarding the impact of host metabolic changes on the intracellular amastigote life stage. Here, we performed cell-based studies to elucidate the interplay between infection with intracellular T. cruzi amastigotes and host cellular energy metabolism. T. cruzi infection of non-phagocytic cells was characterized by increased glucose uptake into infected cells and increased mitochondrial respiration and mitochondrial biogenesis. While intracellular amastigote growth was unaffected by decreased host respiratory capacity, restriction of extracellular glucose impaired amastigote proliferation and sensitized parasites to further growth inhibition by 2-deoxyglucose. These observations led us to consider whether intracellular T. cruzi amastigotes utilize glucose directly as a substrate to fuel metabolism. Consistent with this prediction, isolated T. cruzi amastigotes transport extracellular glucose with kinetics similar to trypomastigotes, with subsequent metabolism as demonstrated in 13C-glucose labeling and substrate utilization assays. Metabolic labeling of T. cruzi-infected cells further demonstrated the ability of intracellular parasites to access host hexose pools in situ. These findings are consistent with a model in which intracellular T. cruzi amastigotes capitalize on the host metabolic response to parasite infection, including the increase in glucose uptake, to fuel their own metabolism and replication in the host cytosol. Our findings enrich current views regarding available carbon sources for intracellular T. cruzi amastigotes and underscore the metabolic flexibility of this pathogen, a feature predicted to underlie successful colonization of tissues with distinct metabolic profiles in the mammalian host.

Dataset Information

ERM Proteins Play Distinct Roles in Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi.

Publications

ERM Proteins Play Distinct Roles in Cell Invasion by Extracellular Amastigotes of <i>Trypanosoma cruzi</i>.

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