# Biofilm Lifestyle in Recurrent Urinary Tract Infections
## 4 Biofilm Formation Patterns in Some Clinically Important Uropathogens  
### Escherichia coli  
_E. coli_ is the most common causative agent of both complicated and uncomplicated urinary tract infection in humans (accounting for around 65-75% of total cases), and one of the most common causes of Gram-negative bacteremia in hospitalized patients [14; 19]. The colon represents a natural reservoir of multiple strains of _E. coli_, among which uropathogenic _E. coli_ (UPEC), neonatal meningitis _E. coli_ (NMEC), sepsis-associated _E. coli_ (SEPEC), and avian pathogenic _E. coli_ (APEC) can be found [34; 65]. UPEC is characterized  
Figure 3: Bacterial QS systems in Gram-negative (**A**) two-component signaling, or (**B**) \(\text{Luxd}/\text{LuxR}\)-type QS systems. Gram-positive (**C**) two-component signaling, or (**D**) AIP-binding transcription factor QS systems. AI: Autoinducers, AIP: Autoinducing peptides.  
by multiple virulence factors which allow for adhesion and colonization of the urinary tract epithelium as well as tissue invasion. The initial adhesion of the pathogen to the uroepithelium is a crucial step for initiation of the infection. Adhesion is mediated by fimbrial adhesions, mainly type 1 fimbiae and _P. fimbiae_[47; 66]. These adhesins also play an important role in cytokine induction, tissue inflammation and biofilm initiation [66]. Flagellar motility allows for climbing up the urethra, followed by colonization of the uroepithelium in the urinary bladder [66; 67]. Hemolysin is secreted to induce tissue damage and siderophores are released to sequester iron from the damaged tissues [68]. The overall virulence behavior aims at localized tissue destruction and initiation of biofilm formation. Previous studies have confirmed the positive correlation between hemolytic activity, biofilm formation and higher levels of antimicrobial resistance in UPEC [69]. The infection triggers a strong response from the innate immunity resulting inystitis, neutrophil influx and exfoliation of the superficial bladder epithelial as a defense mechanism [70; 71; 72].  
In response, _E. coli_ would take an alternative strategy by forming intracellular mini biofilm communities within immature epithelial cells, which can be detected by confocal microscopy as small clusters near the nucleus [70]. The intracellular pathway is initiated by bacterial FimH adhesin of type 1 pili, which recognizes uroplakins and integrins receptors on the superficial umbrella cells of the bladder epithelium, followed by activation of the RHO GTPases family and bacterial endocytosis [44]. Once inside the host cell, bacterial cells start to multiply, forming intracellular bacterial communities (IBC) whose formation is mainly responsible for recurrent infections and chronicystitis [31]. Numerous studies also confirmed the role of K1 capsule polysaccharide of _E. coli_ as an essential virulence factor for successful intracellular survival and IBC formation [31]. In later stages, after localized inflammation-triggered exfoliation of the infected layers, bacteria are released from the IBC by exocytosis and infect deeper exposed immature epithelial cells, hence formation of new IBC and persistence of the infection [44].