**6. Classification of urinary tract infection**

ascend against the flow of urine, and adhere to the epithelial layer. *E. coli* that successfully invade the urinary tract harbor a specific factor that enables them to survive. These strains of *E. coli* are commonly named uropathogenic *E. coli* (UPEC). Flagellae are thread-like structures which provide *E. coli* with the ability to move. It has been found to bind to TLR5 [19] and is of importance for the immune response to *E. coli* in UTI in mice [20]. A critical step for UPEC is adhesion to avoid being washed out with the urine and the first step in a series of events leading to infection. The type-1 fimbriae are adhesion factors studied in great detail and are critical for adhesion and invasion of UPEC into bladder cells [21, 22]. They are equipped with a protein on the tip called FimH, which is responsible for the interaction with the host cell [23]. It binds to several structures on uroepithelial cells, the most important being uroplakin IA that coats the facet cells of the bladder [24]. They also bind to β-integrin, which triggers cytoskeleton rearrangement leading to bacterial internalization [25]. In renal epithelial cells, complement factor 3, which is secreted by epithelial cells during infection, can link with type 1 fimbriae to form a complex that interacts with CD46 to promote internalization. Other fimbriae like P fimbriae are connected with kidney

Flagella provide the bacteria with mobility and may interact with the superficial bladder cell through TLR5. Further adhesion is provided by type 1 fimbriae binding to uroplakin 1A or β1-integrin, which also promote internalization into the cell. Complement secreted upon bacterial infection binds to the bacteria and promotes interaction with the bladder through CD46. In the kidney, P fimbriae of the bacteria bind to glycosphingolipids on the surface of renal

The uroepithelium is having a very important property of flexibility by which it will allow filling and emptying of the bladder and at the same time impermeable to fluid and able to cope with the varying pH, osmolality, and toxicity, for example, high ammonium concentration. It is composed of different layers of cells with the umbrella or facet cells lining the lumen are multinuclear, large cells with uroplakin facing the urine. Uroplakins are proteins contributing to the impermeability of the epithelium but can also act as a receptor for type 1 fimbriae on

The important step in the pathogenesis of UTIs is the adherence of uropathogens to the bladder mucosa. Therefore, adhesins (fimbriae) are important virulence factors. Although virulence factors have been distinguished best in *E. coli* (the most common uropathogen), many same principles may be applicable to other Gram-negative uropathogens, for example, Klebsiellae. Type 1 fimbriae mediate the adherence of glycoprotein receptors (uroplakins) on the uroepithelial cells to *E. coli*, whereas P fimbriae bind to glycolipid receptors in the kidney [25].

It is observed that hyperglycemic environment alters immune function in patients with diabetes. Several aspects of immunity may be affected, including polymorphonuclear leukocyte function and adhesion, phagocytosis, and chemotaxis. This may play a part in the pathogenesis of urinary tract infections in patients with diabetes. Lower urinary concentrations of

infection, since they bind to glycosphingolipids on kidney epithelial cells [26].

50 Microbiology of Urinary Tract Infections - Microbial Agents and Predisposing Factors

epithelial cells. Bacterial invasion is further promoted by TLR4 and TLR5.

**5.2. Increased adherence to uroepithelial cells**

the uropathogenic *E. coli* [27].

**5.3. Immune dysfunction**

UTIs are classified based on laboratory data, clinical symptoms, and microbiological findings. Practically, UTIs have been divided into uncomplicated and complicated UTIs and sepsis. The present guidelines give an outline of a tentative improved system of classification of UTI based on various factors as follows: (Guidelines on Urological Infections by European Association of Urology)

