**2.2 Route of infection**

For UPEC to cause infection, the ultimate origin of it is the intestinal tract of the human host which finally acts as a fecal reservoir. Principally apparent in women, the first step is the bacterial colonization of the vaginal introitus and periurethral meatus. Notably, colonization takes place in parallel with the loss of protective vaginal *Lactobacillus* species. This follows ascension into the bladder and adherence to bladder epithelium (uroepithelium). This is followed by UPEC internalization by umbrella cells (it is the outermost layer of the uroepithelium). Inside the bladder cells, most of the bacteria are exocytosed while the minority of them will evade this mechanism gain entrance into the cytosol to form IBCs (intracellular bacterial communities). When these intracellular bacteria stop replicating, they enter another stage known as QIR (quiescent intracellular reservoir) and are behind recurrent UTI episodes.

In this manner, infection of the lower urinary tract has the power to advance to kidneys and enter the bloodstream to cause urosepsis (**Figures 1** and **2**) [3].

#### **Figure 1.**

*Structure of the urinary bladder and urothelium. The urothelium (transitional epithelium) is believed to form vital and essential hurdle to infection that includes mucus glycosaminoglycans retarding adherence of UPEC, infection-resistant umbrella cells and glycoprotein plates known as uroplakins.*

#### **Figure 2.**

*UPEC pathogenesis. UPEC expresses pili systems (Fim H) for adherence to the epithelial cells of the bladder. It follows invasion into the host cell which initiates replication to form IBCs and a subpopulation also undergoes cell elongation (filamentation). Ultimately the epithelial cell is overloaded and UPEC escapes, rupturing open the host cell releasing motile short and elongated cells which can infect neighboring host epithelia to continue the infective cycle.*
