# Biofilm Lifestyle in Recurrent Urinary Tract Infections
## 4 Biofilm Formation Patterns in Some Clinically Important Uropathogens
### Proteus mirabilis  
_P. mirabilis_ is a common uropathogen that accounts for 4-10% of all UTIs, and is considered the second-most-common causative agent of catheter-associated UTIs after _E. coli_, especially in long-term catheterized patients [5; 21; 22; 79]. A characteristic feature of _P. mirabilis_ is its unique ability to form crystalline biofilms that commonly lead to catheter encrustation and blockage and which, in most cases, is accompanied by urine retention and ascending UTIs [80]. In addition, _P. mirabilis_ could express several virulence factors that predispose the occurrence of urinary tract infection. For instance, _P. mirabilis_ can express multiple types of fimbriea and adhesins, including _P. mirabilis_ fimbria (PMF), _P. mirabilis_ p-like fimbria (PMP), mannose-resistant Proteus-like (MR/P) fimbriea, mannose-resistant Klebsiella-like (MR/K) fimbriea, non-agglutinating fimbria (NAF), and ambient temperature fimbria (ATF) [67; 81; 82]. The aim of these multiple types is to be able to adhere to different types of surface materials in different media, giving rise to the bacterium's remarkable stickiness to many surfaces and at different conditions [81].  
The bacterium is known for its remarkable swarming motility, alternating between two main phenotypes: the swimmer and the swarmer phenotypes. The latter is characterized by heavy expression of flagella [79; 83]. The importance of swarming motility in UTIs' development remains controversial. However, it was reported that swarming cells were able to co-express other virulence factors, such as urease, ZapA protease, and hemolysin, which are all upregulated during swarming [67; 84]. These enzymes aim at reflecting maximum tissue damage in order to facilitate invasion and the release of iron and other nutrients [83; 85]. Needless to say, that motility plays an important role in ascending UTI and pyclonephritis that are common in _P. mirabilis_ infections. The bacterium also shows remarkable ability to swarm across catheters made of silicone or latex, hence contributing to CAUTIs [79; 82]. However, some studies reported that non-motile strains of _P. mirabilis_ were able to induce UTI at similar rates to that of motile strains with comparable complications [85; 86].  
Urease secretion is another important virulence factor of _P. mirabilis_; the enzyme results in hydrolysis of urea and release of ammonia, which shifts the pH of urine into an alkaline environment, and subsequent precipitation of calcium and magnesium ions and the formation of urinary stones composed of magnesium ammonium phosphate (struvite) and calcium phosphate (apatite) [82]. The crystals provide a suitable surface for bacterial attachment and biofilm formation in which bacteria thrive and cause more crystal precipitation [79]. Eventually, the crystalline biofilm grows to the level of blocking urine flow through the catheter, and the formation of renal stones in the ureters, bladder and kidneys. The formed stones are directly related to higher rates of recurrent UTIs since they act as a perfect safe haven for the hiding of bacteria from host defenses and antimicrobial activity, as well as a suitable surface for attachment of other bacteria and formation of biofilms of multiple bacterial communities [79; 83; 87]. The stones would also block urine flow, causing urine retention, which further supports bacterial growth and multiplication (no flushing of urine) [79; 83]. Additionally, some studies reported the ability of _P. mirabilis_ to initiate an intracellular lifestyle within the urinary epithelium cells, accompanied by formation of intracellular calcium containing crystals; however, _P. mirabilis_ fails to establish intracellular biofilms like those observed in _E. coli_ UTI [87; 88].