melitten and Gram-Positive-Bacterial-Infections

Melittin is the main component in the venom of the honey bee (Apis mellifera). It has multiple effects including antibacterial, antiviral, and anti-inflammatory activities in various cell types. However, the anti-inflammatory mechanisms of melittin have not been elucidated in Propionibactierium acnes (P. acnes)-induced keratinocyte or inflammatory skin disease animal models. In this study, we examined the effects of melittin on the production of inflammatory cytokines in heat-killed P. acnes-induced HaCaT cells. Heat-killed P. acnes-treated keratinocytes increased the expression of pro-inflammatory cytokines and Toll-like receptor 2. However, melittin treatment significantly suppressed the expression of these cytokines through regulation of the NF-κB and MAPK signaling pathways. Subsequently, the living P. acnes (1 × 10(7) CFU) were intradermally injected into the ear of mice. Living P. acnes-injected ears showed cutaneous erythema, swelling, and granulomatous response at 24 hours after injection. However, melittin-treated ears showed markedly reduced swelling and granulomatous responses compared with ears injected with only living P. acnes. These results demonstrate the feasibility of applying melittin for the prevention of inflammatory skin diseases induced by P. acnes.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Disease Models, Animal; Gene Expression; Gram-Positive Bacterial Infections; Humans; Interleukin-1beta; Keratinocytes; MAP Kinase Signaling System; Melitten; Mice; Mice, Inbred ICR; NF-kappa B; Propionibacterium acnes; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha

The In vitro activities of two antimicrobial cationic peptides, melittin and nisin alone and in combination with frequently used antibiotics (daptomycin, vancomycin, linezolid, ampicillin, and erythromycin), were assessed against clinical isolates of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Enterococcus faecalis. Using the broth microdilution method, minimum inhibitory concentration (MIC) ranges of melittin and nisin against all strains were 2-8 μg/ml and 2-32 μg/ml respectively. In combination studies performed with the microdilution checkerboard method using a fractional inhibitory concentration index of ≤ 0.5 as borderline, synergistic interactions occurred more frequently with nisin-ampicillin combination against MSSA and nisin-daptomycin combination against E. faecalis strains. The results of the time-killing curve analysis demonstrated that the concentration dependent rapid bactericidal activity of nisin, and that synergism or early synergism was detected in most strains when nisin or melittin was used in combination with antibiotics even at concentrations of 0.5 × MIC.

Topics: Anti-Bacterial Agents; Cells, Cultured; Drug Therapy, Combination; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Melitten; Methicillin-Resistant Staphylococcus aureus; Nisin; Staphylococcal Infections; Staphylococcus aureus