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

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.

Antibiotic Resistance Profiles, Molecular Mechanisms and Innovative Treatment Strategies of Acinetobacter baumannii

“…This study demonstrates the potential of these compounds to act against resistant strains [ 251 ]. Intense activity against biofilms have been observed in cecropins identified in Musca domestica [ 252 ], myxinidin isolated from Myxine glutinosa [ 253 ] and in the complex of AMPs (Fly larvae immune peptides) from Calliphora vicina [ 254 ]. Natural AMPs can be a starting point for the biosynthesis of AMPs with similar functions, being an attractive therapeutic option for the prevention and control of A. baumannii infections.…”

Pse-T2, an Antimicrobial Peptide with High-Level, Broad-Spectrum Antimicrobial Potency and Skin Biocompatibility against Multidrug-Resistant Pseudomonas aeruginosa Infection

“…The mRNA expression of inflammatory mediators, such as IL-1␤, IL-6, and TNF-␣, is reportedly modulated during both cutaneous infection and wound closure ( Fig. 8C to E) (15). The mRNA levels of IL-1␤ ( Fig.…”

“…In particular, Pseudomonas aeruginosa is a major causative agent in infections of chronic wounds that greatly delays wound healing (13,14). Acute infection by this bacterium also leads to the production of proinflammatory cytokines and chemokines, such as tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), and IL-6 (13,15). Ideally, skin wound treatment would alleviate inflammation through the control of related cytokines, transcription factors, and other proteins or genes as well as through elimination of the bacteria (15,16).…”

In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus

“…Primary skin infections stimulate inflammatory response which plays an essential role in the defense against pathogens [ 22 ]. This response involves a complex interplay of cytokines and chemokines, such as the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) [ 23 ].…”