Research: Study targets illusive staph bacteria
By Max Martin, MMJC'19
A team of researchers at Schulich Medicine & Dentistry have discovered how the bacteria Staphylococcus aureus induces bloodstream infections by manipulating the immune system.
It’s a remarkable discovery that could lead to much-needed improvements in patient care and aid vaccine development.
Staphylococcus aureus (S. aureus) is a bacterial pathogen responsible for an array of human diseases. S. aureus produces bacterial toxins, including one group called superantigens.
Stephen Tuffs, PhD, a Postdoctoral Scholar with Microbiology and Immunology, led the research and found superantigens support bacterial survival by manipulating the immune response and inhibiting effective clearing of S. aureus.
“S. aureus makes a toxin that can actually turn what is normally a helpful and supportive immune response against us by overacting,” Tuffs explained. “It creates a situation where bacteria can survive and replicate. The toxin produced can switch our immune system from clearing infection to actually creating a reservoir for bacteria.”
Tuffs described the superantigens as “cryptic toxins” because they turn on the body’s immune system, forcing it to produce excessive amounts of what’s called cytokines.
Cytokines affect the growth of blood cells and other cells that help the body's immune responses. A specific cytokine key to the study is the immune signalling molecule interferon gamma, which becomes overproduced by S. aureus superantigens.
“It’s normally helpful, but these toxins are driving too much interferon gamma production, which eventually interferes with the immune response to bacteria,” explained John McCormick, Professor of Microbiology and Immunology. “S. aureus has learned to manipulate our immune system through these toxins, allowing it to survive and produce more severe disease.”
The study – conducted in mouse models that contain specific human genes – found superantigens promote bacterial survival by manipulating the immune response to inhibit effective clearing of S. aureus.
Tuffs said the research shows Staphylococcal superantigens could be critical therapeutic targets for preventing persistent or severe S. aureus infection.
Globally, there are growing concerns about the pathogen’s increasing resistance to antibiotics, making alternative approaches to treatment essential.
“It’s an enormous problem,” McCormick said. “By understanding how these toxins are working in the context of blood stream infections, we may be able to target the toxin, not the bacteria, in treatment protocols.”
Tuffs said specifically targeting the interferon gamma molecule could be an important component in developing an effective vaccine against S. aureus.
As next steps, the team plans to build on their ground-breaking findings and eventually undertake studies to see if the phenomenon can be detected in humans.
“This is something that has been 30 years in the making,” Tuffs said. “For the first time we have really begun to understand this phenomenon at the immune system level.
