**3.1. α-hemolysin**

Among all the toxins, α-hemolysin (HlyA) is very important which is a lipoprotein and belongs to the RTX (repeats in toxin) toxins family [13, 29, 30]. HlyA is a pore-forming toxin and causes inducible nitric-oxide-synthase (iNOS)-mediated cell membrane injury and apoptosis [31]. However, HlyA can lyse erythrocytes and nucleated host cells at high concentration by a process enabling UPEC which may damage the host immune effector cells for gaining enhanced access to the host nutrients and iron stores. But when the concentration is low, HlyA can induce the apoptosis of target host cells and promote the exfoliation of bladder epithelial cells [13, 32, 33]. Besides, HlyA can also contribute to nephropathogenicity, which was proved by infecting mice transurethrally or intravesically with toxin producer and nonproducer isogenic clone pairs of *E. coli* [34]. A recent study showed that HlyA regulates the dephosphorylation of Akt, which is a multifunctional signaling regulator and responsible for controlling inflammatory responses in the host, as well as the cell cycle control [35]. Moreover, HlyA has the role in the increased production of IL-6 and IL-8 by inducing Ca2+ oscillations in renal epithelial cells [36].

by cdtA, cdtB, and cdtC genes, respectively [28]. CDT has DNase I-like enzymatic activity and attacks DNA, while the other bacterial toxins attack the cell membrane or different targets within the cytoplasm [45]. This unique property of attacking DNA damages the target cell

Virulence Factors of Uropathogenic *E. coli* http://dx.doi.org/10.5772/intechopen.79557 13

Some others including cytolysin A and toll/interleukin (IL-1) receptor (TIR) domain-containing protein (Tcp) are also considered as virulence factors in UTIs [46, 47]. The former causes apoptosis of the host cells [47], while the other has the ability to subvert TLR signaling that gives a survival advantage during UTIs [46]. However, Tcp is associated with pyelonephritis but rare in environmental *E. coli*, in fecal flora of healthy children and in less severe forms of UTI [27]. Besides these, Tcp has also the role in the human avoidance system and cytopathic

In addition to these toxins, vacuolating autotransporter toxin (VAT), Shigella enterotoxin-1 (ShET-1) and arginine succinyltransferase (AST) may also contribute to UTIs. VAT has the cytotoxic effect on the bladder and kidney, while the two others are involved in the invasion of the infections [48]. However, VAT is a highly protected immunogenic protein that belongs

Iron is a very important molecule for all living beings, and *E. coli* uses iron for transporting and storing oxygen, DNA synthesis, electron transport, and metabolism of peroxides. But the amount of iron availability is reduced in the host urinary tract during UTIs [49]. In response to this, *E. coli* possesses some multiple functionally redundant systems that mediate iron uptake by secreting low-molecular-weight Fe3+-chelating molecules which are known as siderophores [50]. Iron utilization, mediated by these siderophores, is critical for colonization of the urinary tract by UPEC [51]. There are four distinct siderophore systems found in *E. coli* such as yersiniabactin, aerobactin, enterobactin, and salmochelin [52]. These systems also include some genes such as ent genes encoding enterobactin, iuc genes encoding aerobactin, and iro genes encoding an ent-like system. However, all these systems are expressed under low-iron conditions and are negatively regulated by ferrous iron and the ferric uptake regula-

Aerobactin is a low-weight molecule and a hydroxamate siderophore with a higher Fe3+ binding stability in acidic environments and is maximally produced at low pH [44, 53]. This siderophore extracts Fe3+ from host iron-binding proteins and is taken up through an outer membrane receptor protein [44]. However, aerobactin has many advantages over other siderophores and is formed from the condensation of two lysine molecules and one citrate cata-

lyzed by an enzyme named aerobactin synthase [13, 25, 30].

DNA which results in progressive cell distending leading to cell death [27].

**3.5. Other toxins**

effect on the kidney [48].

**4. Siderophores**

tor Fur [53].

**4.1. Aerobactin**

to the protease family of SPATE [28].
