**3. Toxins of uropathogenic** *Escherichia coli*

UPEC secrete several virulence toxins which are responsible for the damage of the host cells and host inflammatory response. α-hemolysin (HlyA) is the most virulent toxin produced by UPEC. The effects of HlyA in UTIs are dependent on its dosage produced by UPEC. At high concentration, HlyA destroys the erythrocytes and allow UPEC to break through the mucosal barriers, damage immune system, and depletes iron stores of the host [31–34]. At low concentration, HlyA induces cell death in the bladder using proinflammatorycaspase-1/caspase-4. This causes kidney damage and scarring; oscillations of Ca2+; ascension and colonization of ureters and kidney parenchyma in the renal tubule epithelia resulting in the disruption of normal flow of urine [35–38]. The stimulation of *in vitro* production of actin stress fibers and membrane ruffle in a Rho GTPase-dependent manner is enhanced by cytotoxic necrotizing factor 1 (CNF1) produced by many strains of UPEC. This also facilitates the invasion of UPEC into the kidney cells [39, 40]. However, the extensiveness of CNF1 activities in causing invasion-associated pyelonephritis is not well understood and it has different schools of thoughts [41]. CNF1 also causes polymorphonuclear phagocytosis to trigger apoptosis and scarring of the epithelia of the bladder [42]. The uropathogenic specific protein (Usp) is important in the movement of UPEC from the urinary tract to the bloodstream. High prevalence of Usp has been reported UPEC isolated in cystitis, pyelonephritis, and prostatitis [43]. Serine-autotransporter toxin (Sat) secreted by UPEC is toxic to the cell lines of bladder or kidney origin thereby enhancing pathogenesis of UTI [44, 45]. Also, cytolethal distending toxin (CDT) is another toxin secreted by UPEC which is virulent in UTIs [46, 47].
