**4.** *E. coli* **UTI pathogenesis**

frequently difficult to treat, and can cause parenchymal damage to the kidney, leading to renal insufficiency and further complications [1–3]. UTIs impose a substantial burden on society and the health care system in relation to diagnosis, management, lost productivity, morbidity, and sometimes death [4–6]. Furthermore, increasing resistance to therapeutically important antimicrobial agents and the recent emergence of the virulent and multidrug-resistant ST131 clonal group have made UTI management progressively more costly and challenging [7, 8]. Several studies suggest that a greater array of VFs is generally needed to cause more invasive UTIs, although the extent appears to differ according to age and gender. Thus, further studies targeting VFs, which have been proposed as the best target for vaccine development, are needed. A better understanding of UTI pathogenesis, especially for the most common cause

UTIs are mainly caused by bacteria, although fungi and some viruses have also been implicated. Among bacteria, Gram-negative bacteria of the *Enterobacteriaceae* family, including *E. coli, Klebsiella, Enterobacter, Proteus* species, *etc*., are mostly involved. However, some Gram-positive organisms, principally *Staphylococcus aureus, Staphylococcus saprophyticus* and *Streptococcus agalactiae*, also play a role especially among young women. *E. coli* is the dominant causative agent in all patient groups, causing 80–90% of all UTIs [5]. Consequently, *E. coli*

*Escherichia coli* is a normal constituent of the intestinal microbiota of humans and animals [9, 10]. The distinctive *E. coli* strains that cause most UTIs have been designated uropathogenic *E. coli* (UPEC). They possess diverse virulence-associated factors (VFs) that assist them in attaching to, invading, and injuring the host, and include adhesins, toxins, siderophores, protective polysaccharide coatings, invasins, and serum resistance-associated proteins.

Overall, UTI is more prevalent among females than males, attributable to the close proximity of the urogenital tract to the anus in females, the greater length of the male urethra, and the antibacterial activity of prostatic fluid in men [12, 13]. Functional, hormonal, and anatomical changes that occur during pregnancy predispose pregnant women to UTI [14]. UTI during pregnancy can result in devastating maternal and neonatal complications, including maternal sepsis, preterm labor, and premature delivery [14]. Thirty percent of patients with untreated asymptomatic bacteriuria (ASB) develop symptomatic cystitis and up to 50% develop pyelonephritis [13]. ASB is also associated with intrauterine growth retardation and low-birth-weight infants [13]. Up to 27% of preterm births have been associated with UTI in

of UTI, namely *Escherichia coli*, is crucial for treatment and prevention of UTIs.

46 *Escherichia coli* Escherichia coli - Recent Advances on Physiology, Pathogenesis and Biotechnological Applications - Recent Advances on Physiology, Pathogenesis and Biotechnological Applications

serves as a model pathogen for studying UTI pathogenesis.

**3. Epidemiology and risk factors for** *E. coli* **UTI**

The presence and numbers of such VFs predicts *in vivo* virulence [11].

**2. Etiology of UTI**

pregnancy [14].

UTI pathogenesis is a complex process that is influenced by various host biological and behavioral factors, and by properties of the infecting pathogen, including VFs. This presents a challenge in epidemiological studies regarding the role of specific VFs in UTI pathogenesis because of the confounding effect of host factors.

In most noncompromised individuals, the urinary tract is normally sterile, and the entry of exogenous microorganisms is prevented by urine flow, secreted and tissue-associated antibacterial factors, and the bactericidal activities of effector immune cells. In most cases, the host fecal flora is the source of the infecting *E. coli* strain, and spreads via the perineal, vaginal, and periurethral areas to the lower urinary tract (i.e., urethra and bladder) where they may establish colonization [20]. Two hypotheses have been proposed to explain the movement of the organism from the fecal flora to the urinary tract. The prevalence hypothesis holds that the numerically most prevalent *E. coli* clones in the feces will be involved, whilst the pathogenicity theory holds that *E. coli* strains with enhanced virulence potential will be selected [20]. These two mechanisms may not be mutually exclusive, but instead may jointly contribute to UTI pathogenesis [21].

Although the host's fecal flora is the major source of the *E. coli* infecting strain, other proximal external reservoirs of the organism have been described. Community outbreaks of UTI have been reported [22–24], but without any evidence of person-to-person transmission. Foods and water have been proposed as possible vehicles of such outbreaks [22–24]. Specifically, extensive molecular similarities between *E. coli* from retail meat products and healthy or infected humans have been described [22]. Within-household spread of *E. coli* among co-habitating humans and their pets, including between sexual partners, have been confirmed [4, 10, 11]. The VFs of the invading bacteria and the host's defense mechanisms determine the outcome of the infection [25]. A variety of host factors, such as age, gender, pregnancy, or immunological status, may predispose to UTI and allow less virulent pathogens to cause the disease [20]. If the infection is confined to the lower urinary tract, with symptoms such as dysuria and frequency of urination, the infection is referred to as acute cystitis. If the infection spreads to the upper urinary tract with symptoms such as flank pain, fever, and malaise, the infection is defined as an acute pyelonephritis.
