**3.2. Cytotoxic necrotizing factor 1 (CNF1)**

Another virulence factor secreted by *E. coli* named cytotoxic necrotizing factor 1 (CNF1) is also involved in UTIs and stimulates actin stress fiber formation and membrane ruffle formation in a Rho GTPase-dependent manner that results in the entry of *E. coli* into the cells [37]. The toxin has a remarkable effect on the actin skeletal of HEp-2 cells and produces large vacuoles in HEp-2 cells [28]. However, several in vitro and in vivo studies showed that this protein interferes with polymorphonuclear phagocytosis and evokes apoptotic death of bladder epithelial cells and may lead to bladder cell exfoliation and to enhanced bacterial access to underlying tissue [38, 39]. In addition, there is also a possibility of the association of CNF1 with the hemolysin in the virulence mechanism, which is beneficial for the bacteria [28].

#### **3.3. Secreted autotransporter toxin (SAT)**

Secreted autotransporter toxin (SAT) may also be important as a virulence factor for the pathogenesis of UTIs being had a toxin activity against cell lines of bladder or kidney origin. SAT is a serine protease autotransporter which falls within one subgroup of autotransporters recently classified as the SPATE (serine protease autotransporters of *Enterobacteriaceae*) family and associated with pyelonephritic *E. coli* strains [40, 41]. SAT may have the cytopathic activity that results in the damage of the host tissue and may increase the propagation ability of the UPEC. However, this toxin may facilitate entry of pyelonephritogenic strains into the bloodstream resulting from specific damage to the glomeruli and proximal tubules [40].
