Therapeutic utility of antibacterial peptides in wound healing

Abstract

Cationic antimicrobial peptides were first thought to fight infection in animal models by disintegrating bacterial peptides and later by inhibiting bacteria-specific intracellular processes. However, ever increasing evidences indicate that cationic peptides accumulate around and modulate the immune system both systemically and in cutaneous and mucosal surfaces where injuries and infections occur. Native and designer antibacterial peptides as well as cationic peptides, never considered as antibiotics, promote wound healing at every step of cutaneous tissue regeneration. This article provides an introductory list of examples of how cationic peptides are involved in immunostimulation and epithelial tissue repair, eliminating wound infections and promoting wound healing in potential therapeutic utility in sight. Although a few antimicrobial peptides reached the Phase II clinical trial stage, toxicity concerns limit the potential administration routes. Resistance induction to both microbiology actions and the integrity of the innate immune system has to be carefully monitored.

Keywords:

• acne vulgaris
• anti-inflammatory
• burn wounds
• immunostimulation
• macrophage
• re-epithelialization
• skin infections
• toxicity

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Many cationic antibacterial peptides exhibit significantly better protection in animal models of infection than their microbiology activities in vitro would indicate. Frequently, they are successful in eliminating certain bacteria in animals that are resistant to the same peptides in culture media sensitivity assays.

• Cationic peptides recruit macrophages and neutrophils and, in general, stimulate the immune system around the site of infection. Native antimicrobial peptides accumulate at infection sites and are highly expressed at cutaneous and mucosal surfaces that are prone to injury and ensuing microbial infections.

• Native antimicrobial peptides are beneficial effectors of each step of the wound healing process: inflammation (neutrophil and macrophage invasion), tissue formation (angiogenesis and epithelialization) and remodeling.

• In rodent models, cationic peptides show very impressive efficacy in treating wound and burn infections as read by the re-epithelialization of the injury site and the extent and time required for wound closure. Even uninfected wounds heal better if cationic peptides are administered systemically or topically.

• As both pro- and anti-inflammatory properties are observed, in vivo toxicity is a valid concern. Topical and intramuscular administration appears to be the safest treatment modes.

• Another concern is the induction of resistance not only to the various modes of microbiology actions (membrane disintegration, inhibition of protein synthesis and folding, etc.) but also to the integrity of the innate immune system.