# Biofilms: Novel Strategies Based on Antimicrobial Peptides
## 2 Understanding Biofilm Properties  
Properties of biofilm lifestyle have to be considered when peptide strategies are proposed for the prevention of its formation or in general to design promising anti-biofilm agents. Biofilms develop in three phases: initial adhesion, maturation, and dispersion. The first phase is mediated by some host molecules such as albumin, lipids, complements, fibronectin, and by the interactions of some bacterial surface structures such as pili, fimbiae, but is also influenced by the environment, the micro-organisms properties, the material surfaces, and the flow conditions [5; 6].  
The maturation is especially associated with the EPS production, which allows the stabilization of the biofilm. The last phase, the dispersion, corresponds to the release of cells that colonize new sites. Mature biofilms change microenvironment conditions such as pH, oxygen level, and weaken the activity of antibiotics as well as create particular conditions to induce the state of dormant and non-dividing cells called \"persisters\" that are believed to play an important role in resistance.  
The formation of _P. aeruginosa_ biofilms is very frequent in patients with cystic fibrosis, while _S. aureus_ is frequently correlated with wounds and the multi-species biofilms with urinary catheter or cardiovascular devices.  
Recently, it has been reported that the diseases caused by _Candida albicans_ and non-albicans _Candida_ (NAC) spp., such as _C. glabrata_, _C. tropicalis_, _C. krusei_, _C. dubliensis_, or _C. parapsilosis_ are associated with biofilm growth and, in late stages, their biofilms are more resistant to antifungal drugs. _Candida_ biofilm formation is characterized by three development phases which are the early adhesion phase (0-11 h), intermediate phase (12-30 h), and maturation phase (31-72 h). In order to colonize and form biofilms, cells must attach to the surface or host cells becoming more resistant; new formulations, new agents, and combination therapies are urgently needed to prevent adherence and biofilm development [7].  
An effective anti-biofilm agent should act in different environmental niches in order to reach cells in different growth rate, and also persisters. For very resistant biofilms, a combination of an agent acting on metabolic active cells and another one able to act on persisters could represent a valid strategy.  
EPS is the major component of biofilms; it produces an appropriate environment for the bacteria, favors the adhesion cell-to-cell and cell-to-surface but also constitutes a barrier that interferes with the action of antimicrobial agents decreasing their bioactive concentrations. Therefore, good anti-biofilm agents should be able to penetrate the matrix or inhibit the accumulation on the surface. As cells in biofilms can communicate through secretion of molecules known as auto-inducers that control the quorum sensing (QS), a promising anti-biofilm agent could interfere with QS signals favoring biofilm inhibition or dispersion.  
A drug that exhibits all these anti-biofilm properties together is still not available, even if many studies are devoted to design antimicrobial peptides (AMPs) which can display a combination of these features [8; 9].