Molecular Aspects of Effect of Shiga Toxin in Humans - A Review

Abstract

Shiga toxins belonging to a family of structurally and functionally related protein toxins serve as the key virulence factors for pathogenecity of the virulent enteric bacterial strains namely Shigella dysenteriae serotype 1 including Shiga toxin-producing Escherichia coli (STEC). S. dysenteriae type 1 isolates remain major public health concerns due to their widespread outbreaks and the severity of extra-intestinal diseases, including acute renal failure and also affects the central nervous system. Despite practicing improved hygienic conditions and regulating food and drinking water safety, the enteric pathogens are imposing a major threat in the well being of the human society. Shiga toxin on entry into host cells’ endoplasmic reticulum (ER) activates the stress response in ER and inhibits protein synthesis by catalytic inactivation of eukaryotic ribosomes. In many cell types shiga toxins trigger apoptosis. Recent studies have shown that shiga toxins induce autophagy which activates different signaling pathways in toxin-sensitive and toxin-resistant human cells. In this review the molecular basis of Shiga toxins’ effect on host cell leading to manifestation of the infection in affected individuals are discussed with an emphasis on recent findings.