Group A Streptococcus (GAS), the bacterial species famous for sore throat infections, have a secret weapon for circumventing the immune response to bacterial invasion. Characterized for the first time, “S protein” binds the membranes of red blood cells, effectively hiding GAS from the infected host’s immune system.
When the immune system detects bacterial pathogens like GAS in the body, it launches an immune response to address the invasion. This includes immune cells sent to take out bacterial cells via phagocytosis. To prevent friendly fire, the immune system has to have a process in place to know when to leave normal host cells alone in the hunt to target bacterial cells. It seems that GAS populations take advantage of this system to avoid detection by hiding under red blood cells.
GAS may be mostly known for causing sore throats, but infections with this bacterium as the root cause can be much more dangerous, even lethal, including toxic shock syndrome and flesh-eating disease. Experts estimate that every year, 500,000 GAS infections lead to death, out of 700 million infections caused by GAS occurring annually across the globe.
Penicillin is the drug of choice for GAS infections, but it fails too often. Researchers desperately need another treatment option, and lately they have focused their investigative efforts on targeting virulence factors produced by GAS as a survival tactic. This includes S protein and its affinity for binding red blood cell membranes.
Researchers from the present study used an innovative nanotechnology-based technique, biomimetic virulomics, to identify GAS-produced proteins, ultimately revealing S protein. They found that this particular virulence factor is limited to bacteria within the Streptococcus genus.
While studying GAS utilization of S protein, researchers observed significant differences in mortality in mice infected with GAS when the bacterial cells were coated or not coated with red blood cells. When researchers tested a GAS strain modified to lack S protein, they observed reduced bacterial growth and red blood cell binding in human blood. Instead, GAS bacteria were more often targeted by the immune system and destroyed through phagocytosis.
When S protein was absent altogether, the diversity of proteins GAS produced was significantly altered and virulence factors were in general less abundant, which corresponding author David Gonzales says indicates that S protein “co-opts red blood cell membranes for molecular mimicry,” effectively avoiding the immune system’s counterattack.
With S protein clearly characterized as vital for GAS bacteria’s ability to launch effective infections, the task became clear: inactivate S protein to boost host immunity to GAS infection. In response, researchers are now studying how S protein binds red blood cells as well as S protein activity in other types of streptococcal bacterial. The ultimate goal? Use the information to develop a key ingredient for a new vaccine.
Sources: Cell Reports, Cell Press
