New understanding of “superantigens” may lead to improved treatment of staph infection

Staphylococcus aureus bacteria have long been known to cause infections in humans, ranging from mild skin infections and pneumonia to more serious heart infections. In high-income countries, it is the leading cause of a sometimes fatal disease known as infective endocarditis, which involves inflammation of the heart’s valves or lining.

Now, in a new study, researchers at the University of Wisconsin School of Veterinary Medicine describe another way bacteria can cause harm by undermining the body’s ability to heal from these infections.

The findings could point the way to better treatments for infections caused by Staphylococcus aureus, more commonly known as Staphylococcus aureus infection.

S. aureus bacteria produce small toxins called superantigens that bind to the white blood cells and over-activate the immune system, which can cause complications for the circulatory system. A rabbit study published recently in the Achievements of sciencediscovered that a superantigen called SEC (staphylococcal enterotoxin C superantigen) prevents damage blood vessel from healing. It also stops the formation of new branching blood vessels, important for the wound healing process.

“The role of many molecules of the immune system is to make the blood vessels around the infection more permeable so that they can enter and heal the infection,” explains senior author Vilmara Salgado-Pabon, professor of pathobiology. “But when superantigens hyperactivation of the immune system, your blood vessels can leak, leading to low blood pressure and organ dysfunction.”

When an area of ​​the body is injured, it develops tiny, branching blood vessels called capillaries that send nutrients and oxygen to the injured area. Using a so-called aortic root model, the researchers cut small sections of a rabbit’s aortic artery to simulate the injury. These annular slices failed to form new capillaries in the presence of SEC, preventing the vasculature from healing the injury.

The model works well, says Salgado-Pabon, “because it allows us to test the formation of capillaries – which can be difficult – in a laboratory setting, with all the elements you would expect in the body.”

Infective endocarditis disproportionately affects black and indigenous populations, as well as people who are prone to infection, such as the elderly, people with diabetes, and people who smoke.

The disease is responsible for a high in-hospital mortality rate because it progresses very quickly and can cause complications in other organs throughout the body, Salgado-Pabon says.

Over the past 50 years, treatment from infective endocarditis has remained largely unchanged, now consisting of a six-week course of antibiotics or heart surgery to eliminate the infection. The new results offer the potential to develop new and better approaches.

“You could not only neutralize the effects of toxins on the vasculature, but you could also treat patients to improve their vascular health,” says Salgado-Pabon. “By strengthening a patient’s vascular health, you could proactively prevent complications that lead to death.”

Now that the lab has identified this new biological function, it is working to identify the structures and molecules critical to the process, including identifying molecules that SEC interacts with and identifying cellular receptors that respond to the presence of the toxin.