For nearly half a century, little advancement has been made in the research surrounding staphylococcal infective endocarditis – a serious infection of the heart valves that kills around 20,000 Americans each year.
But now, scientists from the University of Iowa claim they have made a major breakthrough in their understanding of this type of heart disease, after having discovered a deadly bacterial toxin responsible for the infection’s lethal effects.
The culprits: Superantigens produced in large amounts by Staphylococcus aureus (staph) bacteria.
The research was led by UI professor Patrick Schlievert, who is most well-known for identifying TSS toxin-1 – the superantigen that causes toxic shock syndrome (TSS). Schlievert said his work with TSS is very closely related to his work surrounding endocarditis.
“We know that a family of superantigens causes TSS,” Schlievert, chair of microbiology at the UI Carver College of Medicine, told FoxNews.com. “…These superantigens produced by staph bacteria – the TSS toxin and another subfamily called staph enterotoxins – we knew that they cause many secondary infections. Since they cause other staph diseases, and they’re highly lethal, we asked, ‘Do they also cause endocarditis?’”
Infective endocarditis typically occurs in people who have had some prior heart valve damage – either from a birth defect, rheumatic heart disease, drug abuse or some other damaging agent. When there is turbulence in the heart valves, an infection can easily develop at the damaged sites. The most common cause of this kind of infection is the Staphylococcus aureus (staph) bacteria.
According to the Centers for Disease Control and Prevention, staph bacteria are the most significant cause of serious infectious disease in the United States.
“The serious aspect (of infective endocarditis) is that half the people will die, and the other half will develop stroke, because pieces of (the) colony of bacteria break off and go into the brain,” Schlievert said. “….People will develop left side paralysis. A significant percentage, their heart will fail. And then some develop kidney disease and metastatic infections anywhere else…. So it’s the most serious of the staph diseases.”
In order to determine the role superantigens play in this infection, the researchers created two different strains of methicillin resistant staph aureus (MRSA) – one that could produce large quantities of the superantigen staphylococcal enterotoxin C (SEC) and one that could not. After injecting these strains in rabbits with heart valve damage, they found that the SEC-producing strains were capable of causing endocarditis, while the strains that didn’t create SEC could not trigger the illness.
Furthermore, Schlievert and his team showed that by immunizing the rabbits against SEC and passively giving them the antibody to combat the superantigen, the animals were protected against the infection.
SEC ultimately causes the devastating effects of infective endocarditis by entering the bloodstream and prompting an excessive immune system response to the site of the infection. The superantigens also cause low blood pressure and direct toxicity to the cells lining the heart.
“Now we know that this is an important molecule to target,” Schlievert said. “Before there was not a clearly defined target to go after….We have developed a staph vaccine we think will work that targets these molecules, and we hope physicians will try this to decrease case-related death.”
Schlievert said that a combination of their vaccine and antibiotics could potentially eradicate the infection in the body. The antibiotics would help to destroy the staph bacteria in the heart, while the antibodies would destroy the superantigens lingering in the bloodstream. Currently, patients with infective endocarditis only take antibiotics, which do little to prevent stroke and death.
“We’re on the way to being able to do something about managing this disease,” Schlievert said.
The research was published online in the open-access journal mBio.