"We have high affinity molecules that neutralize superantigens and we have previously shown in experimental animals that we can actually prevent strokes associated with endocarditis in animal models. Likewise, we have shown that we can vaccinate against the superantigens and prevent serious disease in animals," Schlievert says.
"The idea is that either therapeutics or vaccination might be a strategy to block the harmful effects of the superantigens, which gives us the chance to do something about the most serious complications of staph infections."
The UI scientists used a strain of methicillin resistant staph aureus (MRSA), which is a common cause of endocarditis in humans, in the study. They also tested versions of the bacteria that are unable to produce superantigens. By comparing the outcomes in the animal model of infection with these various bacteria, the team proved that the lethal effects of endocarditis and sepsis are caused by the large quantities of the superantigen staphylococcal enterotoxin C (SEC) produced by the staph bacteria.
The study found that SEC contributes to disease both through disruption of the immune system, causing excessive immune response to the infection and low blood pressure, and direct toxicity to the cells lining the heart.
Low blood flow at the infection site appears to be one of the consequences of the superantigen's action. Increasing blood pressure by replacing fluids reduced the formation of so-called vegetations plaque-like meshwork made up of cellular factors from the body and bacterial cells -- on the heart valves and significantly protected the infected animals from endocarditis. The researchers speculate that increased blood flow may act to wash away the superantigen molecules or to prevent the bacteria from settling and accumulating on the heart valves.
|Contact: Jennifer Brown|
University of Iowa Health Care