**10. Biofilm production by UPEC**

CNF-1 prevalence of 64% among UPEC isolates from prostatitis and 36% from pyelonephritis. These results suggest that CNF-1 is associated with increased virulence in UTI pathogenesis. CNF-1 production may also increase the inflammatory response of the host [90]. Specifically, Elliott et al. reported that CNF-1 evokes edema and necrosis and is associated with inflammation in the intestines of rabbits in a diarrhea model of infection [90]. Human neutrophils have been observed to be less effective at killing CNF-1 positive, than CNF-1 negative bacteria.

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

UPEC also express outer membrane proteins, such as traT and Iss, which may enhance serum resistance through avoidance of complement killing [26]. Bacteria are killed by normal human serum through the lytic activity of the complement system [91]. The alternative pathway is activated by bacteria in the absence of specific antibody and plays a more important role in serum killing than the classic pathway [92]. Resistance of *E. coli* to killing by serum results from the individual or combined effects of capsular polysaccharide, O-polysaccharide side

Although the K1 capsule is important in certain strains, other mechanisms appear to be more significant determinants of serum resistance in some populations of *E. coli* isolates. On the whole, smooth strains are more serum resistant than rough strains [94] and the degree of serum resistance is proportional to the amount of lipopolysaccharide (O antigen) the strain contains [95]. Serum-resistant strains are usually more nephropathogenic than comparable serum-sensitive strains in a variety of models of UTI [96, 97] even though these resistant

Outer membrane protease T (OmpT) of *E. coli* is a surface membrane serine protease and is the prototypical member of the omptin family of Gram-negative bacteria [98]. OmpT is an enzyme that catalyzes the activation of plasminogen to plasmin [99, 100], a function that is physiologically relevant for the virulence of *Yersinia pestis* and for clinical *E. coli* isolates [101, 102]. OmpT also plays a role in virulence by cleavage of protamine and other cation peptides with antibiotic activity [103, 104]. Studies by Hui et al. indicated that OmpT promotes *E. coli* persistence in the urinary tract by interfering with the antimicrobial activity of urinary

Uropathogenic specific protein (Usp) in *E. coli*, which was discovered by chance, is encoded by *usp* located on PAIs [105]. Usp, which is homologous to the *Vibrio cholerae* zonula occludens toxin gene [106], is significantly more prevalent among UPEC isolates than fecal *E. coli* isolates from healthy individuals. Several studies have shown various roles for Usp in UTI pathogenesis in different UTI syndromes and patient groups. Studies by Rijavec et al. showed

**9. Protectins**

chains, and surface proteins [93].

**9.1. Outer membrane protease T**

cationic peptides [100].

**9.2. Uropathogenic specific protein**

strains may not be associated with increased lethality [96].

Biofilm production by *E. coli* is an important VF which may also protect bacteria from antibiotic action and so contribute to resistance [110–113]. Recent studies have shown that biofilm production in *E. coli*, mediated by co-expression of curli and cellulose, supports long-term survival of UPEC in the urinary tract by surrounding the organism with an inert, hydrophobic extracellular matrix [110, 113, 114]. Most studies of biofilm formation in UTI have addressed its role in recurrences.

Curli belong to a class of fibers known as amyloids and are involved in adhesion to surfaces, cell aggregation and, finally, biofilm development. Curli fibers are encoded in the curling subunit gene (*csg*) gene cluster, made up of two differently transcribed operons. One operon codes for *csgB, csgA*, and *csgC*, and the other one for *csgD, csgE*, and *csgG* [115]. Expression of both curli operons is important for curli fiber assembly. Curli fibers are also essential for internalization of bacteria during an infection [30].

Co-expression of curli and cellulose tends to decrease in prevalence from more severe to less severe UTI, then to commensal isolates, suggesting that biofilm may facilitate progression from the lower to upper urinary tract [110]. Furthermore, co-expression of both biofilm components is associated with a high prevalence of individual VF genes, high VF scores, and phylogenetic group B2, consistent with heightened urovirulence of such strains. Notably, there may be an interaction between classic VFs and biofilm formation. For example, in one study, all isolates that co-expressed both biofilm components also harbored fyuA, implying that iron uptake via the yersiniabactin system may play a significant role in biofilm growth [64]. Additionally, recent studies have shown that the biofilm components, curli fimbriae and cellulose, also play important roles in adhesion, invasion, and long-term survival of UPEC within the host urinary tract [110, 111].
