**9. Protectins**

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 chains, and surface proteins [93].

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

### **9.1. Outer membrane protease T**

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 cationic peptides [100].

### **9.2. Uropathogenic specific protein**

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 a strong association between Usp and bacteremia of urinary tract origin, suggesting that Usp is important in the migration of UPEC from the urogenital tract to the blood stream [107]. Other studies have shown comparable prevalences of Usp in cystitis, pyelonephritis, and prostatitis isolates [108]. Furthermore, Usp has (frequently) been associated with all common serotypes of UPEC [109].
