Abstract
Antimicrobial peptides have been evaluated as possible alternatives to traditional antibiotics. The translational potential of the antimicrobial peptide DGL13K was tested with focus on peptide toxicity and in vivo activity in two animal models. DGL13K was effective against Pseudomonas aeruginosa, Staphylococcus aureus and methicillin-resistant S. aureus with minimal bactericidal concentrations similar to the minimal inhibitory concentration. The peptide showed low toxicity to human red blood cells and HEK cells with median lethal dose around 1 mg/ml. The median lethal dose in greater wax moth larvae (Galleria mellonella) was about 125mg/kg while the peptide caused no skin toxicity in a mouse model. A novel high-throughput luminescence assay was used to test peptide activity in infected G. mellonella, thus reducing vertebrate animal use. DGL13K killed P. aeruginosa in both the G. mellonella model and a mouse burn wound infection model, with bacterial viability 3-10-fold lower than in untreated controls. Future experiments will focus on optimizing peptide delivery, dose and frequency to further improve the antibacterial effect.
Highlights
Traditional antibiotics are losing their effectiveness due to increasing bacterial resistance
The activity of LGL13K and DGL13K was confirmed against Gram-negative P. aeruginosa, whereas only DGL13K was active against Grampositive S. aureus and a methicillin-resistant strain of S. aureus (Table 2)
We chose an antimicrobial peptide (AMP) that is in clinical use, but which is known to lack activity against Gram positive bacteria (Table 2)
Summary
Traditional antibiotics are losing their effectiveness due to increasing bacterial resistance. A recent European estimate attributes 33,100 deaths in 2015 to drug-resistant bacterial infections [4]. On this background, antimicrobial peptides (AMPs) have been evaluated as possible alternatives to traditional antibiotics for over 30 years [5]. Second generation AMPs have largely addressed these concerns and several are in clinical development [8, 9]. Second-generation AMPs appear to provide more robust antibacterial activity under in vivo conditions [9, 10]
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