A Bioengineered Wasp Venom Peptide with Antimicrobial and Anti-Inflammatory Functions

Area of Science:

• Biochemistry
• Pharmacology
• Wound Healing

Background:

• Antimicrobial resistance (AMR) poses a significant public health threat, especially in diabetic foot ulcers (DFUs) where pathogens resist conventional antibiotics.
• Biofilm-producing bacteria in DFUs complicate treatment, necessitating novel therapeutic approaches.

Purpose of the Study:

• To investigate the multifunctional therapeutic potential of PMM4, a novel wasp kinin derivative.
• To evaluate PMM4's antimicrobial efficacy, antioxidant, anti-inflammatory, and anti-hyperglycaemic properties.
• To assess PMM4's cytotoxicity and biocompatibility.

Main Methods:

• PMM4 was synthesized and tested for antimicrobial activity, α-amylase inhibition, DPPH radical scavenging, and albumin denaturation inhibition.
• Cytotoxicity was evaluated using MTT assays with Vero cells and hemolytic assays with erythrocytes.
• Zebrafish embryo toxicity was assessed following OECD TG 236 guidelines.

Main Results:

• PMM4 demonstrated broad-spectrum bacteriolytic activity (MICs 5-10 μg/mL) with minimal hemolysis (<3% at 30 μg/mL).
• The peptide exhibited significant antioxidant (DPPH IC₅₀ = 70.8 μg/mL), anti-amylase (IC₅₀ = 73.7 μg/mL), and anti-inflammatory (IC₅₀ = 60.8 μg/mL) effects.
• PMM4 showed low toxicity, with >95% zebrafish embryo survival at ≤36 μg/mL (LC₅₀ > 60 μg/mL) and ≥85% Vero cell viability up to 625 μg/mL.

Conclusions:

• PMM4 exhibits a dual mechanism of action, including membrane disruption and potential (p)ppGpp binding.
• The peptide offers metabolic and host-modulatory benefits crucial for diabetic wound healing.
• PMM4 is a promising multifunctional therapeutic peptide with broad-spectrum activity, good biocompatibility, and potential for managing infected diabetic wounds.