Abstract
Shiga toxins (Stxs), also known as Shiga-like toxins (SLT) or verotoxins (VT), constitute a family of structurally and functionally related cytotoxic proteins produced by the enteric pathogens Shigella dysenteriae type 1 and Stx-producing Escherichia coli (STEC). Infection with these bacteria causes bloody diarrhea and other pathological manifestations that can lead to HUS (hemolytic and uremic syndrome). At the cellular level, Stxs bind to the cellular receptor Gb3 and inhibit protein synthesis by removing an adenine from the 28S rRNA. This triggers multiple cellular signaling pathways, including the ribotoxic stress response (RSR), unfolded protein response (UPR), autophagy and apoptosis. Stxs cause several pathologies of major public health concern, but their specific targeting of host cells and efficient delivery to the cytosol could potentially be exploited for biomedical purposes. Moreover, high levels of expression have been reported for the Stxs receptor, Gb3/CD77, in Burkitt’s lymphoma (BL) cells and on various types of solid tumors. These properties have led to many attempts to develop Stxs as tools for biomedical applications, such as cancer treatment or imaging, and several engineered Stxs are currently being tested. We provide here an overview of these studies.
Highlights
Shiga toxins are named after Dr Kiyoshi Shiga, the Japanese bacteriologist who first described the dysentery bacillus, Shigella dysenteriae, in 1897 [1]
A broader mechanism, known as the glycolipid–lectin (GL-Lect) hypothesis, has been described for Shiga toxin (Stx) internalization. This model is based on the demonstration that the binding of Stxs, via the three binding sites of the B subunit, to several Gb3 molecules located in lipid rafts induces a reorganization of the plasma membrane, leading to a strong clustering of the Gb3/Stxs complexes eventually resulting in tubular membrane invaginations [18,19,20]
We have shown that the Ramos Burkitt’s lymphoma (BL) cell line expresses activated expresses p38 mitogen-activated protein kinases (MAPKs) and in basal andinduces that Stx1 induces no p38
Summary
Shiga toxins are named after Dr Kiyoshi Shiga, the Japanese bacteriologist who first described the dysentery bacillus, Shigella dysenteriae, in 1897 [1]. A broader mechanism, known as the glycolipid–lectin (GL-Lect) hypothesis, has been described for Stxs internalization This model is based on the demonstration that the binding of Stxs, via the three binding sites of the B subunit, to several Gb3 molecules located in lipid rafts induces a reorganization of the plasma membrane, leading to a strong clustering of the Gb3/Stxs complexes eventually resulting in tubular membrane invaginations [18,19,20]. These studies have shown that the internalization of some galectins—a class of lectins that bind to galactose- and N-acetylactosamine-containing motifs—requires a similar mechanism.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
