**3. Toxins**

Several toxic substances or proteins secreted by uropathogenic strains of *E. coli* play a consequential role as virulence factors in UTIs. However, toxins have the ability to alter the host cell signaling cascade and modulate inflammatory responses. Several in vitro and in vivo studies showed that toxins also contribute to the stimulation of the host cell death and releasing of necessary nutrients, which provide the ability to access deeper tissues within the urinary tract [27]. In 1987, CDT toxin (cyclomodulins) was first reported as virulent toxin in UPEC [28] which opened a new door in the study of the pathogenesis of UTIs, and then many other toxins in UPEC were reported including α-hemolysin (HlyA), cytotoxic necrotizing factor 1 (CNF1), secreted autotransporter toxin (SAT), cytolysin A, plasmid-encoded toxin (PET), vacuolating autotransporter toxin (VAT), Shigella enterotoxin-1 (ShET-1), arginine succinyltransferase (AST), etc.
