A murine model of Staphylococcus aureus infected chronic diabetic wound: A new tool to develop alternative therapeutics

Abstract

Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL-17A compared to control mice that resulted in an IL-17/IFN-γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL-10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL-10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL-10/IFN-γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.