Fundamental study of development of new antibiotics using defensins

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1. Plectasin is the first defensin-like peptide to be isolated from fungus, which has specific antibacterial activity against Streptococcus pneumoniae. In addition, it showed no cytotoxicity to human cells, and it did not induce IL-8 production in A549 cells. This suggests that plectasin could be an inoffensive alternative antibiotic for clinical application. 2. Human α-defensins contribute to excessive mucus production by increasing the production of MUC5AC from bronchial epithelial cells. Macrolide antibiotics directly inhibit these actions. 3. Human α-defensins mainly enhanced the expression of IL-8 in epithelial cells, whereas it enhanced transforming growth factor-β and vascular endothelial growth factor expressions in lung fibroblasts. These results suggest that humanα-defensins play different roles in the pathogenesis of idiopathic pulmonary fibrosis and diffuse panbronchiolitis according to the location in the lung where the humanα-defensins are mainly produced. It is possible that these effects of humanα-defensins carry a risk of adverse effects. Therefore we should examine the possibility of fungal defensins like plectasin as antibiotics.