**3. Virulence factor**

As already we know, STEC is a zoonotic pathogen that is responsible for severe outbreaks worldwide. The main virulence factor of STEC is the production of Shiga toxins 1 and 2. There are additional factors like plasmid-encoded enterohemolysin (EhxA), an autoagglutinating adhesin (Saa), a catalase-peroxidase (KatP), an extracellular serine protease (EspP) that can damage the intestinal tissue or even some factors related to the adhesion to bovine colon like intimin which can induce a characteristic histopathological lesion defined as "attaching and effacing" (A/E) [7–9].

Shiga toxins are encoded by *stx1* and *stx2* genes which are carried by lysogenic phages. They belong to the family of AB5 protein, contains active A subunit and 5 B subunits responsible for binding to cellular receptor available in organs as kidney, brain, liver, and pancreas [10].

These toxins that are produced in colon besides causing local damage can travel via bloodstream to its's target organs such as kidney and play an important role in causing HC and HUS (**Figure 1**) [11].

The damaged caused by toxins is because of inhibition of protein synthesis which leads to apoptosis of endothelial cells [12].

Stx-phages are highly mobile genetic elements which can be transferred through horizontal gene transfer to other *Enterobacteriaceae* [13].

The expression of these genes (especially *stx2*) is affected by environmental conditions such as stress and temperature [14, 15].

The whole cluster of other virulence factors is encoded by chromosomal region called the locus of enterocyte effacement (LEE) presents in many STEC strains, which are responsible for the attaching and causing lesions. In a large proportion of STEC, a plasmid encoding several putative virulence factors like hemolysin can also be found [16].

#### **Figure 1.**

*The effects of Stx in STEC-HUS caused by enterohemorrhagic* E. coli*. GIS, gastrointestinal system; Gb3, globotriaosylceramide; Stx, Shiga-toxin.*
