In-depth characterization of antibacterial activity of melittin against Staphylococcus aureus and use in a model of non-surgical MRSA-infected skin wounds.

Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) require the development of new and effective topical antibiotics. In this context, melittin, the main component of apitoxin, has a potent antibacterial effect. However, little is known regarding the anti-inflammatory potential this peptide in infection models, or its ability to induce clinically important resistance. Here, we aimed to conduct an in-depth characterization of the antibacterial potential of melittin in vitro and evaluate the pharmaceutical potential of an ointment containing melittin for the treatment of non-surgical infections induced by MRSA. The minimum inhibitory concentration of melittin varied from 0.12 to 4 μM. The antibacterial effect was mainly bactericidal and fast (approximately 0.5 h after incubation) and was maintained even in stationary cells and mature MRSA biofilms. Melittin interacts synergistically with beta-lactams and aminoglycosides, and its ability to form pores in the membrane reverses the resistance of vancomycin-intermediate Staphylococcus aureus (VISA) to amoxicillin, and vancomycin. Its ability to induce resistance in vitro was absent, and melittin was stable in several conditions often associated with infected wounds. In vivo, aointment containing melittin reduced bacterial load and the content of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1 beta. Collectively, these data point to melittin as a potential candidate for topical formulations aimed at the treatment of non-surgical infections caused by MRSA.