**1. Introduction**

Urinary tract infections (UTIs) are considered the most frequent bacterial infections in humans usually caused by *Enterobacteriaceae*. Among them, *Escherichia coli* is a predominant etiological factor of UTI [1]. The pathogenic *E. coli* strains belong to different pathotypes including enteric *E. coli* and extraintestinal *E. coli* (ExPEC). Seven major pathotypes of enteric *E. coli* cause mainly

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gastroenteritis but sometimes are responsible for diseases outside the intestinal tract [2]. Three pathotypes of the ExPEC are able to exist in the gut but do not cause diseases in this place. Whereas, colonization by the ExPEC strains of other host niches including the central nervous system, blood, and the urinary tract leads to illness in human [3]. Among ExPEC, uropathogenic *E. coli* (UPEC) is the most frequently associated with human diseases. UPEC strains cause 80–90% of community-acquired UTIs and more than 30% of hospital-acquired UTIs [4]. Development of UTIs depends on anatomical factors of host, defense mechanisms, and virulence factors of infecting microorganism. Bacterial infections of the urinary tract are important problem, because about 60% of women in the United States will have at least one UTI during their life. About 8 million physician visits per year are related to these often chronic infections, making UTIs a problem of economic and medical significance [5]. UPEC can colonize the bladder and cause cystitis or may ascend into the kidneys, causing pyelonephritis [3]. *E. coli* may also spread from the urinary tract to the bloodstream causing bacteremia in above 30% of cases and the potential sepsis [6]. The presence of high numbers of *E. coli* in the urine without the clinical symptoms is referred as asymptomatic bacteriuria (ABU) and such infection in healthy, nonpregnant women is generally not treated [7]. Infections of the urinary tract occur when *E. coli* enter through the urethra and effectively colonize the bladder. *E. coli* is the most common pathogen causing cystitis, pyelonephritis with the possibility of causing kidney damage and death. This microorganism can induce acute renal failure and in case of complications after renal transplantation, *E. coli* is the most common clinical isolate [8]. It is considered that human intestinal tract is a primary reservoir of UPEC strains, although in some cases, clonal group of UPEC strains can be transmitted by contaminated food [9]. Host inflammatory responses on the breach of the sterile urinary tract by UPEC consist of the production of cytokines and chemokines, neutrophil influx, the exfoliation of infected bladder epithelial cells, and the generation of reactive nitrogen and oxygen species [5]. Genomic differences among UPEC and other *E. coli* show evolutionary adaptations, which enable UPEC to colonize environmental niches within the urinary tract such as epithelia lining the lumenal walls of the urethra, bladder, renal pelvis, and collecting ducts of the kidneys [10].

pathways that promote bacterial invasion [15]. Bacterial adherence to urothelium is important in the development of UTI because it allows the bacteria to persist in the urinary tract against flushing by urine flow. Function of type 1 fimbriae as virulence factors in human pathology remains unclear because they are expressed in both commensal and pathogenic *E. coli* strains [16, 17]. The type 1 fimbriae are heteropolymeric surface organelles that consist of several subunits. These fimbriae bind *E. coli* cells to the urothelial mannosylated glycoproteins uroplakin by subunit FimH, which is located at the distal tip of the type 1 fimbriae. UPEC commonly expresses FimH that efficiently bind monomannose- and trimannose-containing glycoprotein receptors. Whereas, commensal *E. coli* strains usually bind to trimannose residues [18]. Binding of FimH to uroplakins that are expressed in the differentiated urothelium of the bladder and urethers causes adhesion and cellular invasion of *E. coli* and promotes formation of intracellular bacterial communities which leads to the acute stage of infection [19, 20]. FimH adhesin enables UPEC to escape before the immune response by internalization within urothelial cells. Inside infected urothelial cells, *E. coli* is harbored within vesicles [21, 22]. Blocking of FimH adhesin with antibodies or inactivity of the *fimH* gene has a negative effect on the ability of UPEC to colonize the bladder epithelium [5]. *fimH* gene is the most commonly iden-

Virulence Factors and Innovative Strategies for the Treatment and Control of Uropathogenic *Escherichia coli*

http://dx.doi.org/10.5772/67778

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About 80% of UPECs express P fimbriae that are frequently associated with acute pyelonephritis [23]. P fimbriae are encoded by *pap*A-K gene operon which can be localized on one or more pathogenic-associated islands [24]. The P-fimbrial–tip adhesins (PapG adhesins) bind to Gal *α* (1–4) Gal in glycosphingolipids of the membrane of urothelial cells localized in the kidney. The PapG adhesins are encoded by four classes of *papG* genes but only two of them are associated with uropathogenicity. Class II adhesin genes are predominant among the isolates from pyelonephritis and from renal transplant patients, while class III genes are found more frequently among cystitis isolates [25–27]. Attachment of P fimbriae to receptors leads to activation of the immune cell response and to the development of inflammation- and painassociated with UTIs. P fimbriae improve bacterial colonization of the tubular epithelium that can adversely affect renal filtration leading to total obstruction of the nephron and conse-

S fimbriae of *E. coli* bind to sialyl galactosides occurring in the receptors of erythrocytes and renal tubular epithelium cells, and are also involved in UTIs development. S fimbriae show binding to epithelial cells of lower urinary tract and kidney and may facilitate bacterial dis-

*E. coli* strains harboring operons coding fimbrial Dr and afimbrial Afa adhesins are also associated with UTIs. Dr adhesins bind to decay-accelerating factor (DAF) which is widely distributed along the urinary tract and plays an important role in colonization of urinary tract by Dr adhesin-producing *E. coli* [29]. UPECs with Afa adhesins have a tropism to renal tissue and have the ability to induce chronic or recurrent infection [30]. The research recently conducted by Muenzner et al. [31] showed that uropathogenic *E. coli* strains, which express the Dra/AfaE adhesins, bind to CEACAMs (carcinoembryonic antigen-related cell adhesin molecules) present on epithelial cells. The interaction of CEACAMs with Dra/AfaE adhesins causes increase of integrin activity, promote matrix adhesion, and suppress epithelial exfoliation, which pro-

tified virulence gene in the isolates causing UTI [17].

semination within host tissues [15, 28].

motes host infection.

quently contributes to the full pathophysiology of pyelonephritis [14].

UPEC strains have different virulence factors that enable the bacteria to adhere and colonize the uroepithelial cells and to establish the UTIs. UPEC harbor more genes encoding adhesins, iron acquisition systems, and toxins than K12 strains and commensal *E. coli* isolates. These virulence genes are often encoded on mobile genetic elements called pathogenicity islands [11, 12].

This paper describes key virulence factors of UPEC, the role of biofilm formation by UPEC in development of UTIs and in catheter-associated UTIs. The resistance to antibiotics and new therapeutic approaches of treatment and control of UPEC will be also discussed.
