The bodies of people with uncontrolled diabetes appear to be the perfect environment for a common type of superbug to thrive unchecked and do its worst damage, according to new research.

The researchers report in Science Advances that Staphylococcus aureus--a bacteria that often is resistant to antibiotics--thrives in glucose-rich diabetic conditions, which trigger it to activate some of its most virulent features. A lack of insulin prevents the immune system from responding to the infection.

"This explains why a wound or cut in a patient with diabetes really must be treated aggressively," said senior author. "The immune system needs help recognizing and clearing the infection before it's able to take hold."

Among people with diabetes, up to a third develop diabetic foot ulcers, which are the most common reason for foot infection and leg amputation, according to the American Diabetes Association. S. aureus most often is associated with these types of invasive infections, especially in people with poorly controlled diabetes.

Rates of S. aureus infections and diabetes have grown in lockstep over the past three decades.

Previously, lead author had shown that S. aureus had evolved an additional two "glucose transporters" on top of the two already common to most staphylococcal species. This gives S. aureus an advantage over other bacteria in making use of excess blood sugar to proliferate.

In this recent study, the team experimented with diabetic and non-diabetic mice and strains of staphylococcus with and without the extra transporters.

In the diabetic mice, the strain of S. aureus with four glucose transporters quickly formed biofilms and activated pathways to make it more virulent. Meanwhile, the immune system of those diabetic mice was particularly slow to respond, resulting in unchecked infection and severe diabetic ulcers. In the nondiabetic mice, the immune system was able to contain and fight the infection. When the diabetic mice were given a drug that lowers blood sugar, they contained the infection almost as well as the regular mice.

Diabetic mice infected with strains of staphylococcus that didn't have the extra glucose transporters had less invasive infections, though their immune systems were still slower to respond than those of their nondiabetic counterparts.

Knowing the mechanism that S. aureus uses to cause such devastating infections in people with diabetes could lead to treatments that capitalize on the bacteria's hunger for glucose, tricking it into consuming a toxic analogue, said the senior author.

"But we also can't lose sight of the need to prevent and control diabetes," the author added. "If we can keep people from developing diabetes and help people who have it to control their blood sugar, then S. aureus will have a much more difficult time causing such terrible infections."

https://advances.sciencemag.org/content/6/46/eabc5569

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