Efficacy of the designer antimicrobial peptide SHAP1 in wound healing and wound infection
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Infected wounds cause delay in wound closure and impose significantly negative effects on patient care and recovery. Antimicrobial peptides (AMPs) with antimicrobial and wound closure activities, along with little opportunity for the development of resistance, represent one of the promising agents for new therapeutic approaches in the infected wound treatment. However, therapeutic applications of these AMPs are limited by their toxicity and low stability in vivo. Previously, we reported that the 19-amino-acid designer peptide SHAP1 possessed salt-resistant antimicrobial activities. Here, we analyzed the wound closure activities of SHAP1 both in vitro and in vivo. SHAP1 did not affect the viability of human erythrocytes and keratinocytes up to 200 μM, and was not digested by exposure to proteases in the wound fluid, such as human neutrophil elastase and Staphylococcus aureus V8 proteinase for up to 12 h. SHAP1 elicited stronger wound closure activity than human cathelicidin AMP LL-37 in vitro by inducing HaCaT cell migration, which was shown to progress via transactivation of the epidermal growth factor receptor. In vivo analysis revealed that SHAP1 treatment accelerated closure and healing of full-thickness excisional wounds in mice. Moreover, SHAP1 effectively countered S. aureus infection and enhanced wound healing in S. aureus-infected murine wounds. Overall, these results suggest that SHAP1 might be developed as a novel topical agent for the infected wound treatment.
KeywordsAntimicrobial peptides SHAP1 Wound healing Infected wound treatment Protease resistance Cytotoxicity
This work was supported by the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Science, ICT & Future Planning (2011-0031955) and the Medicine & Bio Project for “New Drug Development through Fostering of Med-Bio Hub” of the Chungcheong Leading Industry Office (CCLIO) and Ministry of Knowledge Economy (MKE) (C2110907).
Conflict of interest
The authors declare that they have no conflict of interest.
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