Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers

Abstract

Diabetic foot ulcer (DFU) is a devastating complication, affecting around 15% of diabetic patients and representing a leading cause of non-traumatic amputations. Notably, the risk of mixed bacterial–fungal infection is elevated and highly associated with wound necrosis and poor clinical outcomes. However, it is often underestimated in the literature. Therefore, polymicrobial infection control must be considered for effective management of DFU. It is noteworthy that antimicrobial resistance is constantly rising overtime, therefore increasing the need for new alternatives to antibiotics and antifungals. Antimicrobial peptides (AMPs) are endogenous peptides that are naturally abundant in several organisms, such as bacteria, amphibians and mammals, particularly in the skin. These molecules have shown broad-spectrum antimicrobial activity and some of them even have wound-healing activity, establishing themselves as ideal candidates for treating multi-kingdom infected wounds. Furthermore, the role of AMPs with antifungal activity in wound management is poorly described and deserves further investigation in association with antibacterial agents, such as antibiotics and AMPs with antibacterial activity, or alternatively the application of broad-spectrum antimicrobial agents that target both aerobic and anaerobic bacteria, as well as fungi. Accordingly, the aim of this review is to unravel the molecular mechanisms by which AMPs achieve their dual antimicrobial and wound-healing properties, and to discuss how these are currently being applied as promising therapies against polymicrobial-infected chronic wounds such as DFUs.

Wound healing approach based on excretory-secretory product and lysate of liver flukes

“…Antimicrobial peptides are known to play an important role in innate immune response. Activation of innate immune system leads to antimicrobial peptides production, including by skin www.nature.com/scientificreports/ epidermis keratinocytes 54 . Potential exogenous stimulation of O. felineus helminth defense molecule 1 keratinocytes can serve as a nonspecific trigger of wound healing.…”

Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics

“…Generally, AMPs destroy pathogens by attacking and permeabilizing their membranes but there are some AMPs that kill their targets via different mechanisms such as modulation of membrane fluidity, and inhibition of intracellular pathways such as DNA replication and protein synthesis [356,357]. AMPs have been studied as promising new therapies to combat infections and some of them are even in clinical trials [358,359]. In one cell-culture based study, LL-37 (also known as cathelicidin) or cecropin(1-7)-melittin A(2-9) amide (CAMA) AMPs were shown to reduce the minimum biofilm eradication concentrations (MBEC) against biofilm P. aeruginosa by 8-fold [360].…”

Roxadustat, a HIF-PHD inhibitor with exploitable potential on diabetes-related complications

“…The diabetic wound healing process is slower than in non-diabetics. Foot ulcers are very common among diabetic patients and are one of the most serious complications of diabetes, with approximately 15% of diabetic patients suffering from diabetic foot ulcers (DFU) and more than 15% of DFU patients having to undergo surgery for subsequent amputation, which can lead to a relatively high mortality rate (Da Silva et al, 2021). The survival rates of DFU patients at 1, 2 and 5 years are 80.80%, 69.01% and 28.94%, respectively, which seriously affect the quality of life and even threaten life, and bring heavy burden to families and society (Brennan et al, 2017).…”