Biofilm-forming bacteria may be 10−1000 times more resistant to antibiotics than planktonic bacteria and represent about 75% of bacterial infections in humans. Antibiofilm treatments are scarce, and no effective therapies have been reported so far. In this context, antibiofilm peptides (ABPs) represent an exciting class of agents with potent activity against biofilms both in vitro and in vivo. Moreover, murine models of bacterial biofilm infections have been used to evaluate the in vivo effectiveness of ABPs. Therefore, here we highlight the translational potential of ABPs and provide an overview of the different clinically relevant murine models to assess ABP efficacy, including wound, foreign body, chronic lung, and oral models of infection. We discuss key challenges to translate ABPs to the clinic and the pros and cons of the existing murine biofilm models for reliable assessment of the efficacy of ABPs.

Objectives The number of bacterial pathogens resistant to the currently available antibiotics has dramatically increased, with antimicrobial peptides (AMPs) being among the most promising potential new drugs. In this study, the applicability and mechanisms of action of Pa-MAP 2 and Pa-MAP 1.9, two AMPs synthetically designed based on a natural AMP template, were evaluated. Methods Pa-MAP 2 and Pa-MAP 1.9 were tested against a clinically isolated multidrug-resistant (MDR) Escherichia coli strain. Biophysical approaches were used to evaluate the preference of both peptides for specific lipid membranes, and bacterial surface changes imaged by atomic force microscopy (AFM). The efficacy of both peptides was assessed both in vitro and in vivo. Results Experimental results showed that both peptides have antimicrobial activity against the E. coli MDR strain. Zeta potential and surface plasmon resonance assays showed that they interact extensively with negatively charged membranes, changing from a random coil structure, when free in solution, to an α-helical structure after membrane interaction. The antibacterial efficacy was evaluated in vitro, by several techniques, and in vivo, using a wound infection model, showing a concentration-dependent antibacterial effect. Different membrane properties were evaluated to understand the mechanism underlying peptide action, showing that both promote destabilization of the bacterial surface, as imaged by AFM, and change properties such as membrane surface and dipole potential. Conclusions Despite their similarity, data indicate that the mechanisms of action of the peptides are different, with Pa-MAP 1.9 being more effective than Pa-MAP 2. These results highlight their potential use as antimicrobial agents against MDR bacteria.