10/07/1402
Eradication of vancomycin-resistant Staphylococcus aureus on a mouse model of third-degree burn infection by melittin: An antimicrobial peptide from bee venom
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 to 2 μg/mL’ and ‘0.125 to 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
1640 μg, in a single dose. No dermal toxicity and in vivo hemolysis were
observed in the examined41 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.