The growing number of microbial pathogens resistant to available antibiotics is a serious life-threat. Among them, is the bacterium Staphylococcus aureus which colonizes keratinocytes, the most abundant cell type in the epidermis. Its intracellular accumulation complicates treatments against resulting infections, mainly due to the limited diffusion of conventional drugs into the cells. Temporins A (Ta) and B (Tb) are short-sized frog skin antimicrobial peptides (AMPs). Despite extensive studies regarding their antimicrobial activity, very little is known about their activity on infected cells or involvement in various immunomodulatory functions. Here we show that Tb kills both ATCC-derived and multi-drug resistant clinical isolates of S. aureus within infected HaCaT keratinocytes (80% and 40% bacterial mortality, respectively) at a non-toxic concentration i.e. 16 μM, whereas a weaker effect is displayed by Ta. Furthermore, the peptides prevent killing of keratinocytes by the invading bacteria. Further studies revealed that both temporins promote wound healing in a monolayer of HaCaT cells with a front speed migration of 19 μm/h and 12 μm/h for Ta and Tb, respectively. Migration is inhibited by mitomycin C and involves the EGFR signaling pathway. Finally, confocal fluorescence microscopy indicated that the peptides diffuse into the cells. By combining antibacterial and wound healing activities, Ta and Tb may act as multifunctional mediators of innate immunity in humans. Particularly, their non-endogenous origin may reduce microbial resistance to them as well as the risk of autoimmune diseases in mammals.
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|Titolo:||Temporins A and B stimulate migration of HaCaT keratinocytes and kill intracellular Staphylococcus aureus.|
|Data di pubblicazione:||2014|
|Appartiene alla tipologia:||01a Articolo in rivista|