Lack of nutritional immunity in diabetic skin infections promotes <i>Staphylococcus aureus</i> virulence

Abstract

Elevated blood/tissue glucose is a hallmark feature of advanced diabetes, and people with diabetes are prone to more frequent and invasive infections with <i>Staphylococcus aureus.</i> Phagocytes must markedly increase glucose consumption during infection to generate and oxidative burst and kill invading bacteria. Similarly, glucose is essential for <i>S. aureus</i> survival in an infection and competition with the host, for this limited resource is reminiscent of nutritional immunity. Here, we show that infiltrating phagocytes do not express their high-efficiency glucose transporters in modeled diabetic infections, resulting in a diminished respiratory burst and increased glucose availability for <i>S. aureus</i> We show that excess glucose in these hyperglycemic abscesses significantly enhances <i>S. aureus</i> virulence potential, resulting in worse infection outcomes. Last, we show that two glucose transporters recently acquired by <i>S. aureus</i> are essential for excess virulence factor production and the concomitant increase in disease severity in hyperglycemic infections.