## 2 Results and Discussion
### Microbial Focus
to these AMPs or ciprofloxacin at sub-effective concentrations for more than 30 days increased the MIC for ciprofloxacin by 64-fold, the MIC for the AMPs remained unchanged, suggesting that no resistance will be developed to these peptides [58]. Jelleine was first isolated from the royal jelly of bees, with novel analogues being developed by [PERSON] et al., indicating almost no toxicity yet 'potent' inhibition of biofilm formation against MDR _P. aeruginosa_[59]. Established _P. aeruginosa_ biofilms in cystic fibrosis possess extracellular DNA that can be degraded by Gaduscidin-1, thereby helping eliminate existing biofilms. This metal-AMP can also be used synergistically with ciprofloxacin and kanamycin [60], [PERSON] et al. investigated the antimicrobial activity of in silico designed DP7 against 104 clinical _P. aeruginosa_ isolates (57 of which were MDR). The AMP was able to inhibit growth, reduce biofilm formation in vitro, and provide a 70% protection rate and 50% reduction in bacterial colonization in chronic biofilm mouse infection models [61]. _Staphylococci_  
Most publications focused on _S. aureus_, one of the major causes of skin, gastrointestinal, respiratory tract, and blood stream infections. Additionally, biofilms formed by _S. aureus_ are among the most frequent causes of catheter-related or implant-related infections. Human AMP LL-37 appeared to require a 'quite high' antimicrobial concentration with MIC values of 132.3 mg/L and 89.6 mg/L for MRSA and methicillin-sensitive _S. aureus_ (MSSA), strains, respectively [62]. As previously mentioned for _P. aeruginosa_, [PERSON] et al. showed that stably infected Caco-2 intestinal cells expressing HBD-2 and HBD-3 also show antibiofilm activity against _S. aureus_, indicating that therapeutic strategies that enhance endogenous cellular AMP production might be successful as antibiofilm therapy [56]. Mutation of the innate defense regulator peptide (IDR-)1018 (1018M) showed activity against MRSA with a 78.9% reduction in biofilm compared to the original peptide and increased binding to the ppGpp stringent response molecule by 27.9% [63]. From non-human sources, the milk-derived AMP BCp12 was shown to bind to accessory gene regulator (agr) QS proteins of _S. aureus_, potentially useful in the food industry [64]. MPX from wasp venom showed activity against _S. aureus_ and in a skin scratch model was found to reduce _S. aureus_ colonization, thereby resulting in decreased wound size, the promotion of wound healing, and a reduction in inflammation [65]. vCPP2319, a polycationic peptide derived from the Torque virus capsid protein, exhibited activity against established biofilms by killing biofilm embedded bacteria but had no effect on the EPS matrix [66]. The frog skin-derived AMP brevinine-1E-OG9, its analogue (brevinine-1E-)OG9e-De-NH2 [67], and temporin G [68] as well as the synthetic AMP SAMP-A4-C8 not only effectively inhibited and eradicated biofilms but also killed the dormant persister cells, herewith counteracting the recalcitrance of _S. aureus_ infections [69]. Both AP7121, produced by _E. faecalis_ CECT7121 [70], and in silico designed 1018-k6 [71] dose-dependently inhibited biofilm formation on inert surfaces. Furthermore, the AMPs temperorin A, citropin 1.1, and CA(1-7)M(2-9)NH2 were shown to eradicate established biofilms formed on either polystyrene surfaces or central vein catheters [72]. Finally, in two interesting studies, [PERSON] et al. demonstrated that AMPs (HG-1 and halogenan) can be degraded into fragments within hours by the protease aureolysin, secreted by _S. aureus_ bacteria in biofilms to shield themselves from treatment [73], while [PERSON] et al. performed in vitro research involving _S. epidermidis_, showing that many isolates could potentially kill competing nasal microbiota by promoting the production of the AMPs HBD-3 and LL-37 while themselves forming resistant biofilms [74]. _Streptococci_  
A range of Streptococcus were investigated including the major cariogenic species.