*4.1.1 P fimbriae*

Edén and his colleagues discovered in the year 1976 when they identified that *E. coli* that was cultured from pyelonephritis cases attached in more numbers to exfoliated uroepithelial cells when compared to *E. coli* strains obtained from fecal samples [10]. This strong adherence was linked to the presence of 'fimbriae' which when isolated could also specifically adhere to the uroepithelial cell surface [11]. Those bacteria which were expressing this type of fimbria could agglutinate human O erythrocytes and the hemagglutination wasn't been able to be inhibited by mannose hence Mannose Resistant. This kind of agglutination made these new fimbriae distinct from type 1 fimbriae. Later work revealed the receptor to which these new fimbriae i.e., 'P fimbriae' binds is globoseries receptor which is a component of P blood group antigen found in human erythrocytes and uroepithelial cells. Furthermore, this antigen was identified to be a glycospingolipid (synthesized by specific glycosyltransferases and constitutent of glycocalyx surrounding the uroepithelial cells) with a lipid moiety anchored in the cell membrane and a chain of carbohydrates exposed on the erythrocyte surface. These globoseries glycosphingolipid receptors (Gal-Gal) are spread evenly all over the urinary tract especially in kidneys.

P fimbriae are said to increase UPEC virulence at various stages of infection. They help the bacteria to persist longer in the intestinal tract and expand more strongly in the urinary tract with the plan of colonization and going ahead with ascending infection [12, 13]. So, when they reach the urinary tract, *E. coli* strains having P fimbriae attach, persists and even in the presence of enhanced immune response (engaging toll-like receptors 4 and cytokine elaboration) invades kidneys and can cause bacteremia. For the reason, there is a correlation between P fimbriae and acute disease severity in more than 90% of cases. However, <20% asymptomatic carriers also express this P fimbriae. The adhesin complex is encoded by *pap* gene *EFG* sequences.

There exist 3 molecular variants of PapG adhesin encoded by *Pap*G class I through IV alleles, these have different receptor binding preferences ultimately affecting clinical outcomes. For example, allele class II is predominant among strains causing pyelonephritis and bacteremia whereas class III is frequently encountered in women having cystitis and children [14].

## *4.1.2 Type I fimbriae*

Type I fimbriae are considered as a crucial virulent factor in UTI but their exact individual role is challenging to understand as they are expressed by pathogenic as well as commensal strains of *E. coli* including other genera within family enterobacteriaceae. Additionally, it is found that there is an absence of any significant difference in the frequency of the *fim* gene (which encodes type I fimbriae) among more or less virulent strains [15]. These fimbriae are encoded by an operon that contains nine genes present on the chromosome of most of the UPEC in the order of: *fimB, fimE, fimA, fimI, fimC, fimD, fimF, fimG, fimH;* these encoding structural and regulatory proteins [3].

Type I fimbriae bind to uroplakin Ia and IIIa (urothelial mannosylated glycoprotein) through the *FimH* subunit [4]. *FimH* is a tip protein of type I fimbriae. In addition, it may also bind to other cell-surface proteins such as integrins, fibronectin, Tamm-Horsfall protein (THP), etc. This binding or interaction results in molecular phosphorylation events that are necessary for the stimulation of signaling pathways involved in invasion and apoptosis.

Besides, playing a role in attachment to bladder epithelium, it is also found to directly trigger invasion by UPEC into epithelial cells of the bladder (BECs) where they induce formation of IBCs and remain as reservoirs to act as a source of clinical relapse [16, 17]. Some studies have given an insight to the fact that type I fimbriae enhance the infectious potential of UPEC [18, 19] but the accurate timing of expression of fimbria during urinary tract infection remains blurred. It was also seen that UPEC isolates obtained from clinical samples (urine) during infection expressed little to no type I fimbriae [20]. In addition, fimbrial expression was more or less absent in UPEC strains from the urine of women with cystitis [21].

The expression of these fimbriae is finely regulated attending to environmental signals and is under the control of phase variation that determines the percentage of fimbriated cells in the population.

Hultgren and colleagues, in the experimental murine model of UTI, found out that *E. coli* which was obtained from bladder lumen did not express type I fimbriae, however, bacteria that were adhered to the bladder wall did express them*.* Therefore, their contribution in adherence and colonization cannot be effectively determined by measuring the expression of fimbriae in the bladder lumen [22]. There is also an observation that type I fimbriae are not especially prevalent in pyelonephritogenic strains and adherence of bacteria to urinary catheters is also type I fimbriae dependent.

#### *4.1.3 Dr adhesins*

The Dr adhesin family consists of both fimbrial and afimbrial adhesins on *E. coli* surface. There are four genes i.e., *dra A, B, C, D* which encode for adhesins and structural proteins. These adhesins can bind to Dr blood group antigen (a component of decay-accelerating factor which prevents lysis by complement). Inside the urinary

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

tract, they attach to the epithelium of the bladder and type IV collagen present on the basement membranes. Although, these adhesins are present in less number in UTIcausing strains, however collective data from various sources shows that the genes encoding for Dr adhesin family are widespread among cystitis and pyelonephritis strains when compared to control strains (fecal isolates). In the experiments involving mouse models, Dr adesins exhibits tropism for the basement membrane of the renal intersititum, hence integral for chronic pyelonephritis development. Their presence has been linked to epithelial invasion. Some studies in rat models also points out that their interaction with the host cell receptors in kidneys is very much persistent. In addition, it also has a role in the pathogenesis of UPEC as evident in a mouse model study where Dr-positive strain leads to a disease pathologically similar to chronic tubulointerstitial nephritis and a Dr-negative isogenic mutant causes no disease. Type I fimbriae and Dr adhesin together are associated with invasion of epithelial cells of bladder along with intracellular persistence by UPEC [23, 24].
