Abstract
Shiga toxins (Stxs) are classic bacterial toxins and major virulence factors of toxigenic Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC). These toxins recognize a glycosphingolipid globotriaosylceramide (Gb3/CD77) as their receptor and inhibit protein synthesis in cells by cleaving 28S ribosomal RNA. They are the major cause of life-threatening complications such as hemolytic uremic syndrome (HUS), associated with severe cases of EHEC infection, which is the leading cause of acute kidney injury in children. The threat of Stxs is exacerbated by the lack of toxin inhibitors and effective treatment for HUS. Here, we briefly summarize the Stx structure, subtypes, in vitro and in vivo models, Gb3 expression and HUS, and then introduce recent studies using CRISPR-Cas9-mediated genome-wide screens to identify the host cell factors required for Stx action. We also summarize the latest progress in utilizing and engineering Stx components for biomedical applications.
Highlights
Shiga toxin (Stx) was named after Japanese microbiologist Kiyoshi Shiga, who identified and characterized Shigella dysenteriae in 1897 [1]
Toxicity differences among Stx subtypes are partially ascribed to differences in receptor binding, and it is believed that the low dissociation rate of Stx2a with receptors may lead to greater toxicity due to longer toxin uptake [52]
The results indicate that LAPTM4A is specific to Stx, whereas TMEM165 and TM9SF2 are required for ricin [64]
Summary
Shiga toxin (Stx) was named after Japanese microbiologist Kiyoshi Shiga, who identified and characterized Shigella dysenteriae in 1897 [1]. Among Shigella dysenteriae strains, serotype 1 is the toxigenic one that expresses Stx [2]. It was soon realized that these toxins belong to the same Stx family and can be divided into two serotypes: Stx is almost identical to the prototype Stx in Shigella dysenteriae, while Stx shares ~56% protein sequence identity with Stx [5]. In the United States, there are approximately 265,000 cases of EHEC infection [6], which usually starts with diarrhea and can develop into dysentery and hemorrhagic colitis. HUS is most commonly associated with EHEC serotype O157:H7 infections, and Stx is the major cause [7]. We will briefly introduce the mode of action for Stx and focus on the latest progress in identifying host factors and engineering Stx for biomedical applications
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