## 2 Antibofilm Peptides
### Antibofilm Peptides Tested In Vitro  
Within the past decade, a number of peptides have demonstrated excellent antibofilm activity leading to either inhibition or eradication of the biofilm. The selected examples of such peptides are presented in Table 1. One of the first peptides that was discovered to possess antib Biofilm activity was the human cathelcidin LL-37 [42]. LL-37 is one of the most studied AMPs, displaying antib Biofilm activity at sub-inhibitory concentrations (i.e., 16-fold below its minimum inhibitory concentration (MIC) value against planktonic _P. aeruginosa_) [43]. Notably, this peptide has virtually no activity against planktonic bacteria and yet display a biofilm-specific activity. This discovery has triggered the interest to investigate antibofilm properties of synthetic fragments of LL-37 in order to understand the relationships between peptide's structural properties and its mode of action [44]. In one particular study, a peptide library screen for small cationic peptides, derived from LL-37, resulted in identification of a nine-mer antib Biofilm peptide 1037 (KRFRIRVRVR-NH\({}_{2}\)) that inhibited _P. aeruginosa_ biofilm formation by 50% at one-twentieth the MIC [45]. LL-37 analogs were also tested against _Staphylococcus aureus_, where the most active analog P10 demonstrated remarkable activity inhibiting biofilm development and potentially eradicating a preformed biofilm of multi-drug resistant clinical isolate of _S. aureus_[46]. Similarly, the mouse homologue cathelcidin-related antimicrobial peptide(CRAMP) has been able to inhibit fungal biofilm formation [47]. More interestingly, several studies have demonstrated that shorter fragments of CRAMP, such as AS10, still were able to inhibit biofilm growth of _Candida albicans_, while showing no cytotoxicity [48]. Additionally, to antifungal activity, AS10 exhibited inhibitory activity against bacterial biofilms formed by _Escherichia coli_ and _P. aeruginosa_. Human liver-derived antimicrobial peptide hepcidin 20 (hep20) serves as another example of natural peptide with antib biofilm properties. When tested against _Staphylococcus epidermidis_ biofilms, hep20 was able to inhibit biofilm formation [49]. These findings spiked development of various antibiofilm synthetic peptides derived from natural AMPs. For example, innate defense regulator peptide IDR-1018 was derived from bovine neutrophil host defense peptide bactencin and demonstrated broad-spectrum antibiofilm activity against a number of both Gram-positive and Gram-negative pathogens [50]. As a next step, [PERSON] et al. designed and screened a D-eanantiomeric peptide library based on properties associated with IDR-1018 [51]. Resulting two synthetic peptides DJK-5 and DJK-6 displayed broad-spectrum antibiofilm activity and ability to eradicate pre-existing biofilms. [PERSON] and [PERSON] used a different approach and designed a hybrid peptide named CAMA (eccropin (1-7)-melittin A (2-9) amide) that contained the N-terminal region from cecropin A and N-terminal region from melittin A and was highly effective at inhibiting methicillin-resistant _Staphylococcus aureus_ (MRSA) biofilm formation [52]. [PERSON] et al. presented two synthetic tryptophan-rich cationic antimicrobial peptides KT2 and RT2 that demonstrated potency against multidrug-resistant _E. coli_ biofilms at sub-MIC levels. Both peptides were able to prevent biofilm formation and eradicate mature biofilms [53]. In a recent study, [PERSON] and colleagues demonstrated a synthetic ultrashort peptide UP-5 containing only arginine and biphenylalanine that showed potency against _S. aureus_ biofilms [54]. Other interesting examples are described in detail by [PERSON] et al. and [PERSON] et al. [39; 55]. AMPs are known to successfully enhance potency of conventional antibiotics especially against multi-drug resistant strains [56; 57]. Combinational therapy reduces antibiotic concentrations and hence, lowers toxicity and resistance development.