A diabetic mouse model of early stages of Clostridium perfringens -gas gangrene

Since Clostridium perfringens gas gangrene is strongly associated with human diabetes, this study compared gas gangrene severity in db/db (a model for type 2 diabetes) vs wild-type (WT) mice after a 4 h C. perfringens challenge.

Before C. perfringens challenge, glucose and branched chain amino acids (BCAA) concentrations were significantly higher in db/db vs. WT mice. All mice were then inoculated intramuscularly in, i) the left thigh with DPBS containing 10⁶, 10⁷ or 10⁸ washed cells of C. perfringens type A strain ATCC3624 and ii) the right hind thigh with DPBS. After 4 h, mice were euthanized and samples of muscle and subcutaneous tissue from those thighs were collected for anaerobic culture or histology examination.

Gross and microscopic lesions in the left thigh were influenced by bacterial dose. With 10⁷ or 10⁸ bacterial challenges, the db/db mice showed more severe gross and microscopic lesions than did WT mice. No gross or microscopic lesions were observed in the right thigh of any mice. No significant differences were noted in C. perfringens numbers recovered from the left thigh of db/db vs WT mice at any challenge inoculum. After a 2 h challenge, RT-qPCR detected more expression of genes encoding alpha toxin and perfringolysin O in the db/db than in WT mice.

This study supports the usefulness of db/db mice to study C. perfringens gas gangrene pathogenesis in diabetics. It also suggests that higher BCAA and glucose levels and/or stronger upregulation of toxin production in db/db mice may be factors that help cause the development of more severe lesions during the early stages of gas gangrene in the db/db mice.