Eradication of vancomycin-resistant Staphylococcus aureus on a mouse model of third-degree burn infection by melittin: An antimicrobial peptide from bee venom

Abstract

Third-degree burn infections caused by antibiotic-resistant bacteria are of high clinical concern. Chemical antibiotics are not promising in eradication of bacterial infections. In this challenging condition, antimicrobial peptides (AMPs) are recently introduced as novel promising agents to overcome the issue. Accordingly, our study aimed to evaluate the efficiency of ‘melittin’ as natural peptide in bee venom, in eradicating vancomycin resistant Staphylococcus aureus (VRSA) on a mouse model of third-degree burn infection.In vitro pharmacological value of melittin was determined by examining its inhibitory and killing activities on VRSA isolates at different doses and time periods. The action mechanism of ‘melittin’ was evaluated by fluorescent release assay and Field Emission Scanning Electron Microscopy (FE-SEM) analyses. In vivo activity and toxicity of melittin were also examined on a mouse model of third-degree burn infection.The Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) of melittin on all isolates ranged from ‘0.125–2 μg/mL’ and ‘0.125–4 μg/mL’, respectively. Rapid antibacterial activity of melittin on VRSA isolates was demonstrated by killing kinetics assays. Fluorometric and FE-SEM analyses indicated the membranolytic effects of melittin on VRSA isolates. The colonized VRSA bacteria were eradicated by melittin at 16 μg, in a single dose. No dermal toxicity and in vivo hemolysis were observed in the examined mice.The lack of in vivo toxicity of melittin along with its potent antibacterial activity indicated its promising therapeutic value as a topical drug against S. aureus associated third-degree burn infections.