# Biofilm Lifestyle in Recurrent Urinary Tract Infections
## 4 Biofilm Formation Patterns in Some Clinically Important Uropathogens
### Candida albicans  
_C. albicans_ is a dimorphic fungus that is a common inhabitant of normal flora in skin and mucous membranes. It is also an opportunistic bacterium that takes advantage of immunosuppression to cause candidiasis in different tissues: the oral cavity, GIT, genitourinary tract, the ears, the bones, the eyes, wounds and blood [28; 95]. Risk factors of urinary tract candidiasis increase with prolonged catheterization, age, female gender, intensive care admission, diabetes, prosthetic devices and implants, obstructive uropathy, neonates, and prolonged antibiotic treatment [27]. _C. albicans_ is the leading cause of fungal urinary tract infections and accounts for up to 25% of all CAUTIs and 10-20% of all nosocomial infections with significant risk of development into a systemic infection with high mortality rates [11; 27]. The pathogenicity of _C. albicans_ is highly dependent on multiple virulence factors, namely polymorphism, adhesion to both biotic and abiotic surfaces, and biofilm formation [27]. Polymorphism refers to the ability of the fungus to switch between three morphological forms: (i) the yeast form (oval-shaped budding cells which is the normal commensal form and the infective form in virulent strains); (ii) hyphal form (an invasive filamentous form which harbors important adhesins for attachment to other cells, secretes large number of hydrolytic enzymes and plays a pivotal role in biofilm formation); and (iii) septate pseudohydphae (which is a transient form found within mature _candida_ biofilms) [28; 95]. The ability of _C. albicans_ to initiate a pathogenic infection is highly dependent on switching to the filamentous form and on biofilm formation [28]. The initial attachment of the fungus is mediated by two groups of adhesins: the agglutinin-like sequences adhesins (AIS) and the Hyppha-associated GPI-linked protein adhesins (Hwp1) [26; 27]. After adhesion, the yeast cells begin a stage of proliferation and filamentation accompanied by secretion of extracellular matrix material, the filamentous hyphal cells adhering to each other, forming support scaffolds that contribute to the overall mechanical stability of the biofilm [26; 28; 95].  
Moreover, the biofilm matrix material contains the polysaccharides mannan and glucan. The latter plays a critical role inhibiting neutrophil activation and creates a thick physical barrier to prevent the diffusion of drugs. Furthermore, glucan has been proven to bind to amphoteric B, thus restricting its effectiveness [26; 28]. _Candida_ biofilms are associated with high levels of extracellular enzymes secretion, including lipases, esterases, and phospholipipases hemolysis, all of which contribute to pathogenicity by inducing host tissue damage, releasing nutrients and increasing tissue invasion [11; 27; 28]. In addition, _C. albicans_ produces a group of secreted aspartyl proteases (Saps) secreted by the filamentous morphotype, which causes tissue damage allowing for elongation of the filaments and tissue penetration to deeper layers, as well as degrading antibodies and blocking complement activation [28]. Furthermore, _C. albicans_ biofilms are inherently resistant to most known antifungal drugs and show much-reduced sensitivity to amphoteric B, making biofilm-mediated candidiasis difficult to eradicate with high recurrence rates [26; 95].