Abstract

This report shows that the antimicrobial peptide (AMP) Epinecidin-1 (Epi-1) efficiently heals MRSA-infected heat burn injuries and provides protection from infection in a pig model. The presence of an optimal level of Epi-1 induces cell proliferation by promoting cell cycle progression through an increase in S-phase cells. Epi-1 also induces proliferation to cover the wounded region in an in vitro cell proliferation assay using immortalized human epithelial HaCaT cells. Next, the in vivo wound healing efficiency of Epi-1 was tested in heat-burned pig skin infected with MRSA under in vivo conditions. Treatment of the injury with Epi-1 for 1 h at six hours post-infection completely healed the wound within 25 days. Conversely, the injury in the untreated control was not healed 25 days post-infection. Histological staining of wound sections with H&E showed that Epi-1 enhanced vascularization and increased epithelial activities in the wound region. Neutrophil recruitment to the wounded region in the Epi-1-treated sections was visualized by Giemsa staining. Additionally, Masson's trichrome staining of wound sections confirmed that Epi-1 enhanced extracellular collagen compound formation. The induction of sepsis-associated blood C-reactive protein (CRP) and the pro-inflammatory cytokine IL-6 in response to MRSA infection was also suppressed in pigs that received Epi-1. Taken together, the results demonstrate that the biomaterial Epi-1 heals wounds through increasing epithelial cell proliferation, vascularization, and the formation of collagen and controls MRSA infection-mediated sepsis in pigs.

Highlights

  • Infection of bodily injury sites causes morbidity in wounded patients [1]

  • The expression of the epithelial negative cell surface markers connexin (Cx) 43 and keratin 3 (K3) was significantly decreased when the HaCaT cells were treated with 15.625 μg/ml of Epi-1 (Figure 1D)

  • We have demonstrated that Epi-1 exerts potent antimicrobial activity against methicillin-resistant Staphylococcus aureus

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Summary

Introduction

Infection of bodily injury sites causes morbidity in wounded patients [1]. Despite dramatic developments in trauma care and management, wound infections with pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are a major challenge to medical researchers [2]. The pathogen Staphylococcus aureus (SA) is commonly found on the skin and in the noses and throats of the long-term hospitalized and can cause infections through injuries [3]. The emergence of pathogens resistant to available antibiotics for skin wound infections is a major challenge in wound management, and the identification of suitable therapeutic alternative agents to existing antibiotics will minimize the emergence of drug resistance to single antibiotics in cases such as MRSA [5, 6]. Topical administration at the wound region has the advantage of bypassing the need for an intact circulatory system [7, 8]

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