# Biofilm Lifestyle in Recurrent Urinary Tract Infections
## 4 Biofilm Formation Patterns in Some Clinically Important Uropathogens
### Enterococcus faecalis  
_E. faecalis_ is an opportunistic bacterium that is a common member of intestinal flora in humans and animals [14]. _E. faecalis_ is a common causative agent of both community-acquired and hospital-acquired urinary tract infections (UTIs), with high rates of complicated UTI, especially in catheterized patients and patients under prolonged antibiotic treatment with vancomycin or third-generation cephalospororin [32]. The infection is likely to proceed into severe, life-threatening systemic infections in about 15-24% of cases, especially immunocompromised individuals [32]. Pathogenic _E. faecalis_ usually originates from undercooked animal-based food, which is often linked to high rates of antimicrobial resistance due to the extensive use of antibiotics in animal farms [37; 52]. The infectioncan also be transmitted from person to person by orofecal route [37]. _E. faecalis_ is highly associated with CAUTIs, due to its significant ability to form biofilms on urinary catheters. The bacterium takes advantage of the fibrinogen deposition on the catheter surface and uses it as a nutrient source through the production of fibrinogen digestive proteases [89].  
Some of the most important virulence factors in _E. faecalis_ are the surface polysaccharides ride antigens that are essential for the initial attachment and subsequent biofilm formation on urinary catheters, mainly adhesin collagen of _Enterococcus faecalis_ (Ace), enterococcal surface protein (Esp), and enterococcal biofilm associated pili (Ebp). The latter is of special importance, since it contains an N-terminal fibrinogen-binding domain which allows the bacterium to adhere firmly to the fibrinogen-coated catheter surface [37; 89]. Another unique feature of _E. faecalis_ is its ability to suppress the innate immune response at the site of infection. This is contrary to the strong inflammatory response that is expected upon insertion of a foreign body like a urinary catheter in the bladder, a response that is initiated by neutrophils and macrophages [32; 37]. The immune modulating effect of _E. faecalis_ is mediated by the simultaneous action of multiple virulence factors: (i) gelatinase enzyme, whose expression is turned on by QS, cleaves the complement components C3, C3a, and C5a, which inhibits opsonization and neutrophil recruitment, hence inhibiting pathogen labeling for subsequent phagocytosis; (ii) TcpF, a protein that interferes with Toll-like receptor (TLR) activity of leukocytes, hence inhibiting the subsequent initiation of both innate and adaptive immune pathways; and (iii) the aggregation substance (AS), which initiates internalization into macrophages and uroepithelial cells and confers resistance to super oxides, leading to increased intracellular survival within macrophages and bladder epithelium [32; 37; 52]. The overall result of the previous effects is the development of high-titer catheter-associated biofilms, as well as the ability to evade phagocytosis, decrease antibodies production, and survive within macrophages, neutrophils and bladder epithelium for extended periods [89]. Moreover, the immunosuppression at the infection site encourages co-infection with other uptongens, hence promoting polymicrobial urinary tract infection [32]. This explains the general observation that _E. faecalis_ is often found as part of a polymicrobial biofilm community and usually co-isolated with _E. coli_ and other uptongens like _P. aeruginosa_ and _P. mirabilis_, leading to aggravated symptoms and higher risks of complicated UTIs [89]. _E. faecalis_ has intrinsic resistance to trimethoprim, clindamycin, cephalosporporins and penicillins, and lately has been associated with increased rates of resistance to glycoptides, including vancomycin, which is considered a last-resort antibiotic against multidrug-resistant bacteria [14].