## 1 Introduction  
Bacteria form biofilms when growing on surfaces or air-liquid interfaces. Biofilms are structured aggregates of bacteria encased in a protective extracellular matrix that can contain polysaccharides, proteins, extracellular DNA, and lipids [1]. The switch from a free swimming, planktonic to an adherent biofilm lifestyle results in increased adaptive resistance to antimicrobial agents making biofilm-related infections inherently difficult to treat [1; 2]. Apart from colonizing inert materials such as catheters and medical implants, bacterial biofilms are prevalent in chronic infections, such as those that develop in the lungs of cystic fibrosis (CF) patients [3; 4]. CF is the most common eventually fatal autosomal-recessive disorder in Caucasian populations and is caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride-channel, as well as various modifier genes that influence severity. CF patients rapidly acquire lifelong chronic respiratory infections that lead to hyper-inflammation and progressive destruction of lung function [5]. The opportunistic pathogen _P. aeruginosa_ is the most prevalent pathogen associated with lung deterioration in patients with CF [3; 5]. Its high intrinsic resistance and ability to develop biofilms in the CF lung, combined with the lack of specific anti-biofilm therapeutics, seriously hinders the treatment of chronically-infected CF patients, and although _P. aeruginosa_ can initially be transiently suppressed by aggressive antibiotic therapy, the same strain can re-emerge and predominate for years. In fact, it has been suggested that treatment with antibiotics such as tbramycin (used in the treatment of CF), tetracycline, and norfloxacin might contribute to infection chronicity by inducing biofilm formation [6; 7]. During its long-term colonization of the CF lung, _P. aeruginosa_ undergoes several genetic adaptations leading to different colony morphologies [8], some of which are linked to bacterial persistence. For example, mucoid _P. aeruginosa_ strains, which result from mutations within the anti-sigma factor _mucA_, have been associated with biofilm formation [9] and antibiotic resistance [10]. Likewise, small colony variant (SCV) colonies have been shown to be hyper-adherent with reduced susceptibility to antibiotics [11; 12; 13]. Another major factor is the emergence of mutator strains that enable the rapid evolution of resistant strains in the CF lung. The biofilm mode is also associated with resistance to phagocytic killing, which is one of the major mechanisms of clearance in the lung. In addition to _P. aeruginosa_, infection with bacterial species from the _Burkholderia cepacia_ complex (Bcc), a collection of nine genotypically distinct but phenotypically similar species, has been associated with a poor prognosis in CF patients [14, 15]. Cationic host defense (antimicrobial) peptides represent a novel alternative to conventional antibiotics. These peptides, e.g., the human catheelicidin LL-37, often have modest direct antimicrobial activities for planktonic cells [16] and are known to possess immunomodulatory properties [17]. More recently, it has been demonstrated that LL-37 has excellent anti-biofilm activity _vs. P. aeruginosa_ causing a 50% decrease in biofilm formation at one sixteenth the minimum inhibitory concentration (MIC) [18]. Similar results were subsequently shown by other groups [19, 20]. This encouraged the development of improved synthetic cationic peptides with activity against bacterial biofilms [21, 22, 23, 24, 25, 26, 27]. Anti-biofilm peptides are biochemically similar to antimicrobial peptides in that they are short (12-50 amino acids long) and amphipathic, having two to nine basic residues (R or K) and \(\sim\)50% hydrophobic residues [18, 19, 20, 21, 22]; however they exhibit specific activity against biofilms at concentrations often well below their MIC for planktonic cells [18, 19, 20, 21, 22], and there is no correlation between anti-biofilm activity and anti-planktonic cell activity [18].