Abstract
Escherichia coli, one of the most abundant bacterial species in the human gut microbiota, has developed a mutualistic relationship with its host, regulating immunological responses. In contrast, enterotoxigenic E. coli (ETEC), one of the main etiologic agents of diarrheal morbidity and mortality in children under the age of five in developing countries, has developed mechanisms to reduce the immune-activator effect to carry out a successful infection. Following infection, the host cell initiates the shutting-off of protein synthesis and stress granule (SG) assembly. This is mostly mediated by the phosphorylation of translation initiator factor 2α (eIF2α). We therefore evaluated the ability of a non-pathogenic E. coli strain (E. coli HS) and an ETEC strain (ETEC 1766a) to induce stress granule assembly, even in response to exogenous stresses. In this work, we found that infection with E. coli HS or ETEC 1766a prevents SG assembly in Caco-2 cells treated with sodium arsenite (Ars) after infection. We also show that this effect occurs through an eIF2α phosphorylation (eIF2α-P)-dependent mechanism. Understanding how bacteria counters host stress responses will lay the groundwork for new therapeutic strategies to bolster host cell immune defenses against these pathogens.
Highlights
In eukaryotic cells, stress granule (SG) assembly can be induced by several environmental stresses including heat shock, oxidative stress, viral infection and UV irradiation, amongst others [1]
Our first approach was to determine the capacity of non-pathogenic and pathogenic strains of Escherichia coli to induce stress granule assembly in the Caco-2 cells derived from human colorectal adenocarcinoma frequently used to study E. coli [14]
These results suggest that E. coli infection does not induce SG assembly in
Summary
Stress granule (SG) assembly can be induced by several environmental stresses including heat shock, oxidative stress, viral infection and UV irradiation, amongst others [1]. SGs are non-membranous cytoplasmic foci, which are formed by mRNA, 40S ribosomal subunits, translation initiator factors (eIF4E, eIF4G, eIF4A, eIF4B, eIF3, eIF2) and RNA-binding proteins such as TIAR, G3BP1 and HuR [2]. The classical mechanism for SG induction is mediated by phosphorylation of the α subunit of the translation initiator factor 2 (eIF2α) by one of the four stress-responsive kinases: HRI, PERK, GCN2 or PKR [3]. Phosphorylation of eIF2α inhibits protein translation by reducing the exchange of the eIF2-GDP to the eIF2-GTP ternary complex necessary for translation initiation (reviewed in [3]). SGs participate in mRNA stabilization and transport, cell survival and cell death [4] and are associated with the pathogenesis of diseases such as cancer, neurodegenerative diseases, inflammatory disorders and viral infections [5].
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