High glucose levels in the tissue and blood of people with diabetes may help make drug-resistant Staphylococcus aureus infections more aggressive, new mouse research suggests. "The excess blood glucose exacerbates the toxicity of each little MRSA cell, they're just meaner and nastier when they have sugar around them," Dr. Anthony R. Richardson of the University of Pittsburgh, the study's corresponding author, told Reuters Health by phone. Macrophages and neutrophils help fight infections with oxidative bursts that generate reactive oxygen species (ROS) and nitric oxide (NO), Dr. Richardson and his team note in Science Advances. Immune cells need glucose to fuel oxidative burst, and must also express high-affinity glucose transporters-1 and -3 (GLUT -1/-3), while lack of oxidative burst is the leading immune defect in people with diabetes, they add. In lab studies and a streptozotocin (STZ)-induced diabetic mouse model, the researchers found, macrophages could not generate an oxidative burst if glucose was not present, and they did not express GLUT-1 or -3. They also found that S. aureus required both of its glucose transporters (glcA and glcC) for full virulence. Infections were more severe in the STZ-treated mice, which had blood glucose levels of at least 300 mg/dL, versus around 100 mg/dL for the untreated mice. At the site of infection, tissue glucose levels were four times higher in the STZ-treated mice. "The mechanism explaining the requirement of effective insulin signaling for phagocyte GLUT-1/-3 expression remains unknown," the authors note. "That said, we can now begin to understand why patients with diabetes suffer specifically from S. aureus infections so frequently." The findings underscore the importance of maintaining blood glucose control, which can be a challenge for some patients, Dr. Richardson said. "Those patients make up a significant number of patients with diabetes," he added. "You just gotta get that glucose under control, you've got to get that glucose down." —Anne Harding Source
