Using MGN-3 to mediate innate immunity in a diabetic (hyperglycaemic) model of an infected chronic wound

Shah, Sana, El Mohtadi, Mohamed and Ashworth, Jason ORCID: https://orcid.org/0000-0001-7045-7899 (2022) Using MGN-3 to mediate innate immunity in a diabetic (hyperglycaemic) model of an infected chronic wound. In: Microbiology Society Early Career Microbiologists’ (ECM) Forum Summer Conference 2022, 12 July 2022 - 13 July 2022, University of Sheffield, UK.

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Abstract

Background The diabetic foot ulcer (DFU) is a type of chronic wound presenting in type 2 diabetics that frequently becomes infected by polymicrobial communities, leading to significant morbidity and mortality. Antibiotics are used as the first line of defence against DFU infections but over-usage has led to widespread antibiotic resistance. To reduce the reliance on antibiotics, novel therapies are desired that can promote infection clearance by stimulating innate host immune responses, thereby either replacing or working alongside antibiotic intervention. This study investigated the use of Biobran (MGN-3) to mediate innate host clearance of typical 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 treatments 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) culture conditions. The phagocytic ability of M1 macrophage exposed to MGN-3 (0.5, 1.0, 2.0 mg/ml) was compared against bacterial clearance observed in the absence of MGN-3 (untreated control), following treatment with rice starch (0.5, 1.0, 2.0 mg/ml; negative control) and following treatment with bacterial lipopolysaccharide (LPS 5g/ml; positive control). Results Increasing levels of hyperglycaemia significantly (p<0.05) increased the 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) M1-mediated phagocytosis of both MRSA and PAO1 in a dose dependent manner compared to the untreated and rice starch-treated controls. Conclusion MGN-3 significantly reversed the detrimental impact of increasing hyperglycaemia on M1-mediated phagocytosis, highlighting the beneficial effect of MGN-3 on promoting bacterial clearance in a dose-dependent manner under hyperglycaemic conditions. These findings suggest the use of MGN-3 in local wound dressings as a potential cost-effective therapeutic strategy to resolve clinical DFU infections warrants further investigation.