Target intelligence / Profile preview

Shiga toxin gene (stx) (stx)

Target
stx
Molecular classification
Bacterial DNA, Virulence factor
01

Overview

Shiga toxin genes (stx1 and stx2) are the primary virulence factors in Shiga toxin-producing Escherichia coli (STEC), including the O157:H7 serotype [CDC]. These genes are typically located on lambdoid prophages integrated into the bacterial chromosome and are expressed during the lytic cycle [StatPearls]. The encoded Shiga toxins are AB5-type toxins that consist of an enzymatically active A subunit and a pentameric B subunit responsible for cell binding [StatPearls]. Once inside a host cell, the A subunit acts as an N-glycosidase, cleaving a specific adenine residue from the 28S ribosomal RNA, which irreversibly halts protein synthesis and leads to apoptosis [StatPearls]. This cellular damage primarily affects the intestinal mucosa and the vascular endothelium, particularly in the kidneys, leading to hemorrhagic colitis and hemolytic uremic syndrome (HUS) [CDC]. While these DNA sequences are critical for the molecular diagnosis of STEC infections via PCR, they are not traditional therapeutic targets for small molecules or biologics [Nature Reviews Microbiology]. Instead, therapeutic development focuses on neutralizing the toxin protein or inhibiting its binding to host receptors like globotriaosylceramide (Gb3) [Nature Reviews Microbiology]. A significant clinical challenge is that certain antibiotics can induce the bacterial SOS response, which triggers prophage induction and significantly increases stx gene expression and toxin release [Frontiers in Microbiology].

Other names
stx1stx2Shiga-like toxin genesVerotoxin genesvtx
02

Mechanism of action

The stx genes encode Shiga toxins that inhibit host protein synthesis by depurinating the 28S rRNA of the 60S ribosomal subunit [StatPearls].

03

Biological functions

Toxin biosynthesisRegulation of bacterial virulence
04

Disease associations

InfectionHemolytic uremic syndromeHemorrhagic colitis
05

Safety considerations

Antibiotic-induced SOS response leading to increased toxin production [Frontiers in Microbiology]Risk of Hemolytic uremic syndrome (HUS) progressionTherapeutic challenge of targeting intracellular toxins
06

Biomarkers

stx1 DNA sequence detection via PCR [CDC]stx2 DNA sequence detection via PCR [CDC]Shiga toxin protein detection in stool [CDC]

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