Myxinidin2 and myxinidin3 suppress inflammatory responses through STAT3 and MAPKs to promote wound healing.

Hyo Mi Han,Yoonkyung Park,Jeong Kyu Bang,Chang Ho Seo,Tudor Luchian,Min-Ju Cheong,Sujin Ko

doi:10.18632/oncotarget.20908

Abstract

Skin wounds are continuously exposed to bacteria and can easily become infected. Infected wounds require antibiotic treatment, and infections caused by drug-resistant bacteria are an important public health problem. Antimicrobial peptides have broad-spectrum antibacterial activity, induce little or no drug resistance and may be suitable for treating skin infections caused by drug-resistant bacteria. We previously reported the design and function of myxinidin and myxinidin analogues. Here we showed that myxinidin2 and myxinidin3 exhibit antimicrobial and anti-biofilm activities against antibiotic-resistant Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa in high salt environments and in gelatin. Moreover, these peptides facilitated infected wound healing by decreasing inflammation through suppression of IL-6, IL-8, and TNF-α and regulation of downstream mediators such as STAT3, p38, JNK, and EGFR. In a mouse skin wound model infected with antibiotic-resistant bacteria, myxinidin2 and myxinidin3 eliminated the infection and enhanced wound healing. We therefore propose the use of these peptides for treating infected wounds and burns.

Highlights

Bacterial infection of a skin wound can cause wound healing to be delayed and even cause a worsening of the wound
Myxinidin2 and myxinidin3 were evaluated for their antibiotic activity against one gram-positive strain (S. aureus) and two gram-negative species (A. baumannii and P. aeruginosa), including several antibioticresistant strains (Supplementary Figure 1)
Myxinidin2 and myxinidin3 were effective against antibiotic-resistant S. aureus CCARM 3018, A. baumannii 719705, and P. aeruginosa 4076

Summary

Introduction

Bacterial infection of a skin wound can cause wound healing to be delayed and even cause a worsening of the wound. Most wound infections are caused by pathogenic bacteria such as Staphylococcus aureus [1], Acinetobacter baumannii [2], and Pseudomonas aeruginosa [3] Some stains of these pathogens, which can cause acute pneumonia, septicemia, and secondary infections in the brain or in other internal organs, are resistant to antibiotics in part because they form biofilms [4]. Efforts are being made to develop improved dressing materials for wounds, including hydrated biomaterials typically composed of polysaccharides such as gelatin. These biomaterials have numerous advantages in that they are biocompatible, biodegradable, and bacteriostatic, and they induce wound healing similar to that of natural tissues [7]

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