Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2021-12, Vol.11 (12), p.1894
• Main Authors: Da Silva, Jessica, Leal, Ermelindo C, Carvalho, Eugénia
• Format: Article
• Language: English
• Subjects: Anaerobic bacteria; Angiogenesis; Antibacterial activity; Antibacterial agents; Antibiotics; Antifungal activity; Antimicrobial activity; Antimicrobial agents; Antimicrobial peptides; Antimicrobial Peptides - pharmacology; Antimicrobial Peptides - therapeutic use; Antimicrobial resistance; Bacteria; Bacteria - drug effects; Bacteria - growth & development; bacterial and fungal infections; Biofilms; Biological Factors - pharmacology; Biological Factors - therapeutic use; Chronic illnesses; chronic non-healing wounds; Clinical outcomes; Diabetes; Diabetes mellitus; Diabetic Foot - drug therapy; Diabetic Foot - microbiology; diabetic foot ulcers; Drug Resistance, Bacterial - drug effects; Drug Resistance, Fungal - drug effects; Feet; Foot diseases; Fungi; Fungi - drug effects; Fungi - growth & development; Gram-negative bacteria; Gram-positive bacteria; Humans; Hyperglycemia; Hypoxia; Immune system; Inflammation; Leg ulcers; Microorganisms; Molecular modelling; Morbidity; Neutrophils; Pathogens; Peptides; Reptiles & amphibians; Review; Staphylococcus infections; Ulcers; Wound healing; Wound Infection - drug therapy; Wound Infection - microbiology
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11121894

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.