Shiga Toxin (Stx) Classification, Structure, and Function

Abstract

Shiga toxin (Stx) is one of the most potent bacterial toxins known. Stx is found in Shigella dysenteriae 1 and in some serogroups of Escherichia coli (called Stx1 in E. coli). In addition to or instead of Stx1, some E. coli strains produce a second type of Stx, Stx2, that has the same mode of action as Stx/Stx1 but that is antigenically distinct. Because subtypes of each toxin have been identified, the prototype toxin for each group is now designated Stx1a or Stx2a. The Stxs consist of two major subunits, an A subunit that joins noncovalently to a pentamer of five identical B subunits. The A subunit of the toxin injures the eukaryotic ribosome, and halts protein synthesis in target cells. The function of the B pentamer is to bind to the cellular receptor, globotriaosylceramide, Gb3, found primarily on endothelial cells. The Stxs traffic in a retrograde manner within the cell, such that the A subunit of the toxin reaches the cytosol only after the toxin moves from the endosome to the Golgi and then to the endoplasmic reticulum. In humans infected with Stx-producing E. coli (STEC), the most serious manifestation of the disease, the hemolytic uremic syndrome or HUS, is more often associated with strains that produce Stx2a rather than Stx1a, and that relative toxicity is replicated in mice and baboons. Stx1a and Stx2a also exhibit differences in cytotoxicity to various cell types, bind dissimilarly to receptor analogs or mimics, induce differential chemokine responses, and have several distinctive structural characteristics.

Hybrid Shiga Toxin-Producing and Enterotoxigenic Escherichia sp. Cryptic Lineage 1 Strain 7v Harbors a Hybrid Plasmid

“…Two of the STEC/ETEC hybrid strains isolated from humans exhibiting illness, IH53473 and IH57218, express Stx2a, and another, C165-02, expresses Stx2d (Table 1). Interestingly, the remaining two clinical isolates, 3020-98 and MI02-35, one of which was isolated from a patient exhibiting bloody diarrhea, carry the stx 1c subtype, which is rarely isolated from humans and is typically linked to mild disease when it is isolated from humans (49). These two strains reportedly express Stx1 but not ST (12).…”

“…The subtypes linked with serious human disease are stx 1a , stx 2a , stx 2c , and stx 2d (49). Two of the STEC/ETEC hybrid strains isolated from humans exhibiting illness, IH53473 and IH57218, express Stx2a, and another, C165-02, expresses Stx2d (Table 1).…”

Prevalence of Shiga toxin-producing Shigella species isolated from French travellers returning from the Caribbean: an emerging pathogen with international implications

“…They consist of an enzymatically active A subunit that exhibits RNA N-glycosidase activity and a B pentamer which is responsible for binding of the toxin to glycolipid receptors on the target cell surface. After binding, Shiga toxin enters a mammalian cell by endocytosis and eventually traffics to the endoplasmic reticulum where the A subunit is proteolytically cleaved to an inactive, A2 subunit and an active A1 subunit which binds to and inactivates the host cell ribosome [3]. Infections with bacteria that produce Shiga toxin can cause hemorrhagic colitis and lead to more serious complications like hemolytic uremic syndrome (HUS), a potentially deadly condition [4].…”

Overview and Historical Perspectives

“…In chapter 2 (6), Flemming Scheutz describes the taxonomy of STEC and Stx toxins and relates this information to the public health significance of the different serotypes and toxin subtypes. The discussion of Stx toxin continues in chapter 3 where Angela Melton-Celsa reviews the structure and function of these toxins (76). Sadiq and colleagues take a genomic perspective in chapter 4 (41) to review the history of typing and genetic analysis from distinguishing STEC strains using pregenomic methodologies to the current technology, where the genome sequences of multiple strains can be determined in a single day.…”