Research findings could help combat dangerous superbug infections

A new study involving University of Iowa researchers suggests that blocking the action of a toxin produced by almost all strains of the superbug MRSA could lead to better treatments for the life-threatening illnesses caused by these bacteria.

The research team led by scientists at the University of Edinburgh in Scotland identified the new toxin, known as staphylococcal enterotoxin-like X or SElX, and showed that it is produced by 95 percent of all strains of Staphylococcus aureus (“staph”) bacteria including MRSA (methicillin-resistant Staphylococcus aureus).

The study also showed that the toxin causes an extreme overreaction by the immune system leading to high fever, toxic shock, and potentially fatal lung inflammation. The findings appear in the October issue of the journal PLoS Pathogens.

The research, carried out at the universities of Edinburgh, Iowa, Minnesota, and Mississippi State, looked at an emerging strain of community-associated MRSA known as USA300 that can cause severe infections, including skin abscesses and necrotizing pneumonia, in otherwise healthy individuals.

Patrick Schlievert, Ph.D., professor and head of microbiology at the UI Roy J. and Lucille A. Carver College of Medicine and an international expert on bacterial toxins and the toxic shock illnesses they cause, was part of the study team. He describes the work as “a perfect collaboration.”

“The Edinburgh group identified the toxin and showed the toxin was made by the USA300 strains, and we showed the toxin caused serious illnesses,” says Schlievert, who recently moved to the UI from the University of Minnesota where some of the work for the current study was done.

In particular, Schlievert and colleagues showed that staph bacteria that make SElX are lethal in animal studies, whereas the same strain lacking SElX does not cause severe illness including necrotizing pneumonia, a potentially fatal lung infection.

SElX belongs to a family of toxins known as superantigens, which can invoke an extreme immune response. Other superantigens include toxic shock syndrome toxin-1, which Schlievert identified in 1981 as the cause of toxic shock syndrome, and staphylococcal enterotoxin B and enterotoxin C.

“We showed that the SElX has the same activities as toxic shock syndrome toxin-1, namely the ability to cause high fever, low blood pressure and shock, as well as other symptoms of toxic shock syndrome and necrotizing pneumonia,” Schlievert says. “The significance of this new study is that we now know that all staph strains make either toxic shock syndrome toxin-1, SElX, or staphylococcal enterotoxin B and enterotoxin C, all with the capability of causing serious human illnesses.”

Schlievert and colleagues now are studying ways to develop vaccines and other drugs that target bacterial toxins like SElX. Such therapies might provide protection against the life-threatening effects of these toxins.

The research was funded by the Biotechnology and Biological Sciences Research Council, the National Institutes of Health, the US Department of Agriculture, and Pfizer Animal Health.

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