**4.2 Toxins**

There are three main types of toxins that are secreted by UPEC. These are:



#### **Table 2.**

*Summary of various adhesins of UPEC.*

Apart from these, there are other toxins identified which are secreted by UPEC strains and have cytotoxic activity. Toxins production by UPEC leads to inflammatory response causing UTI symptoms.

#### *4.2.1 Hemolysin*

In 1921, Dudgeon *et al.*, documented that 50% of *E. coli* isolates which caused UTI were causing hemolysis on blood agar plates in comparison with 13% of fecal isolates. This action was credited to the hemolysin protein secreted by *E. coli* (belonging to the family of RTX toxins (repeats-in-toxin)) [29]. α-hemolysin (Hly A) is the most vital virulence factor secreted by UPEC that is associated with pyelonephritis. The *hly* genes encode for proteins that are needed to synthesize and secrete hemolysin. This toxin shows dual activity dependent on concentration i.e., low and high concentration:


α-Hemolysin can also result in the elevated elaboration of IL-6 and IL-8 by inducing Ca2+ oscillations in renal epithelial cells. In addition, this toxin is associated with renal complications in 50% of cases of pyelonephritis and also causes endothelial damage and renal vasoconstriction. To add up permanent renal scarring is a usual complication that follows infection by HlyA *E. coli* [31].

## *4.2.2 CNF-1*

CNF-1 is frequently detected in *E. coli* strains causing UTI and almost always in association with hemolysin with which it is linked genetically. This protein is secreted by

#### *Uropathogenic* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.102525*

*E. coli* in vitro and prompts actin stress fibers formation and membrane ruffle formation in a Rho GTPase dependant manner. Various studies describe its potential role in UPEC pathogenesis. CNF-1 appears to increase the attachment of PMNs (polymorphonuclear leukocytes) to T84 monolayers (epithelial cells) theraby decreasing their phagocytic effect. Besides, it leads to apoptosis in the 5637-bladder cell line, an event that might be elucidate the exfoliation of bladder epithelial cells after UPEC infection [32].

## *4.2.3 Autotransporters*

Autotransporters toxins also named as type V secretion toxins consists of SAT (secreted autotransporter toxin) and VAT (vacuolating autotransporter toxin) encoded by UPEC [33]. SAT is demonstrated more commonly among *E. coli* strains (55% strains) associated with pyelonephritis relative to fecal strains (22%). SAT which was first isolated from *E. coli* CFT073 have highest similarity to SPATES (seriene protease autotransporters of Enterobacteriaceae) proteins made by diarrheagenic *E. coli* and *Shigella species*. Experiment shows SAT possess toxic activity against bladder and kidney cell lines and theraby may have an important role in the pathogenesis of UTI.

VAT was originally discovered in avian pathogenic *E. coli.* In addition, there are Pic and Tsh autotransporters recognized. Pic is known to have seriene protease activity while Tsh lacks. These both are seen to be more prevalent in pyelonephritis strains than fecal strains.

Moreover, recent studies have identified other proteins which are secreted by UPEC and known to have cytotoxic activity. These are NRPS (nonribosomal peptide synthases) and PKS (polyketide synthases) which are produced by B2 *E. coli* strains and are involved in arresting cell cycle [3].
