Streptococcal bacteria use an enzyme called streptokinase to block the blood clotting response and allow themselves to move more freely around the human host's circulatory system. The molecule is so specific, it only works on humans, not on other animals.

"The theory is that, as bacteria cause a local infection and begin to grow, the clotting system produces clots in the blood vessels around the infection, closing the highways that the bacteria would use to spread," said David Ginsburg, a research professor at the U-M Life Sciences Institute and a Howard Hughes Medical Institute investigator.

"You can see how one bacterial species and one host get locked in this evolutionary dance and would evolve apart from other host-bacterial pairs---ending up with a multitude of variants of streptococci, one for each host.

"This evolutionary mechanism probably functions for many other pathogenicity factors, not just streptokinase, and probably underlies the species-specificity of all kinds of infectious organisms," Ginsburg said.

"The bacterial streptokinase enzyme bypasses this blood-clotting system by causing the blood clot to dissolve so the bacteria can spread," Ginsburg said. Streptokinase secreted by group A streptococcus works by activating the human form of the enzyme plasminogen, which routinely dissolves blood clots in the body.

Human plasminogen is specific to our species, so U-M postdoctoral fellow Hongmin Sun had to develop a genetically engineering humanized mouse that made significant amounts of human plasminogen to test the researchers' ideas about group A streptococci.

Ginsburg adds that making this mouse susceptible to human-type streptococcus infection
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Contact: Karl Leif Bates
batesk@umich.edu
734-647-1842
University of Michigan
26-Aug-2004