Background
The diabetic foot ulcer (DFU) frequently becomes infected by polymicrobial communities, leading to patient morbidity and mortality. Although antibiotics are the first line of defence against DFU infection, over-usage has led to widespread antibiotic resistance. Given the need for novel therapies to replace or use alongside antibiotic intervention, this study investigated Biobran/MGN-3 as a potential modulator of innate host responses to wound pathogens in a diabetic (hyperglycaemic) model of an infected DFU.
Methods
Host-pathogen interaction assays (n=12) were used to assess the effect of MGN-3 on M1 (classically activated macrophage)-mediated phagocytosis of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa (PA01) under euglycemic (11mM) and hyperglycaemic (15mM, 20mM and 30mM) conditions. The phagocytic ability of M1 exposed to MGN-3 (0.5, 1.0, 2.0 mg/ml) was compared against bacterial clearance in the absence of MGN-3 (untreated control) or following treatment with either rice starch (2.0 mg/ml; negative control) or bacterial lipopolysaccharide (LPS 5mg/ml; positive control).
Results
Increasing levels of hyperglycaemia significantly (p<0.05) increased bacterial recovery by impairing M1-mediated phagocytosis. However, MGN-3 and LPS supplementation reversed the detrimental effect of glucose by significantly increasing (p<0.05) phagocytosis of both MRSA and PAO1 in a dose dependent manner compared to untreated and negative controls.
Conclusion
MGN-3 significantly reversed the detrimental impact of increasing hyperglycaemia on M1-mediated phagocytosis, highlighting the beneficial effect of MGN-3 on innate immune responses. These findings suggest MGN-3 incooperation into local wound dressings as a potential cost-effective therapeutic strategy to treat clinical DFU infections warrants further investigation.