New clues in understanding why group A streptococci (GAS) has a range of bacterial afflictions in humans

Dec 6 2004

Researchers have unlocked new clues in understanding why group A streptococci (GAS) has a range of bacterial afflictions in humans. One of the keys to this species of bacteria is its production of streptokinase (SK), an enzyme that activates plasminogen, the blood clot-dissolving protein in humans.

Findings of the research will be presented today at the 46th Annual Meeting of the American Society of Hematology (ASH). Results of the study suggest that GAS, a group of bacterial organisms that cause a range of infectious diseases, from those as common as strep throat to the wildly virulent and often fatal "flesh-eating" bacterium, attacks soft tissues and internal organs and spreads through the blood stream and surrounding tissues by breaking down the barriers created by local blood clots that could contain the infection.

Streptokinase produced by GAS that infect humans is highly specific for human plasminogen (PLG) and has little or no effect in other mammals. Generating a humanized transgenic mouse that expressed human PLG, the researchers tested for the specificity of the interaction with GAS. When the mice were introduced to GAS they were highly susceptible to infection and mortality was higher compared with the normal mice. The increased susceptibility of mice to GAS, however, was largely abrogated when the SK gene was deleted, leading the researchers to identify the major role of the PLG/SK interaction in the GAS pathogenicity.

"While we don't know exactly why the same bacterium causes such a range of illnesses from mild and harmless to life threatening, our study provides new clues that begin to unlock this mystery," according to Hongmin Sun, Ph.D., University of Michigan Medical School, and lead author of the study. "Most notably, our observations highlight the potential role of infectious disease as a critical force in the evolution of the hemostatic system and the unusual species specificity of many coagulation factor interactions."