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Streptococcus infects humans by thwarting blood clotting

Streptococcal bacteria may infect humans by using a bacterial enzyme to "hijack" the blood-clotting system, according to new research by Howard Hughes Medical Institute scientists.

In studies published in the August 27, 2004, issue of the journal Science, the researchers establish that the enzyme streptokinase is responsible for the pathogen's ability to infect humans while exhibiting little activity against other mammals.

The scientists genetically altered strains of mice to make the animals susceptible to infection by streptococcus. They say their strategy outlines a new path for developing animal models for human-specific microbes. The research is also likely to open the way to new understanding of the factors that enable bacteria to evolve host specificity, the researchers said.

Howard Hughes Medical Institute investigator David Ginsburg led the research team, which included lead author Hongmin Sun and colleagues at the University of Michigan and Lund University in Sweden.

"Understanding why bacteria in general are so species-specific has been a major problem for a long time," said Ginsburg. "And this species-specificity had greatly hindered our ability to develop an animal model for human-specific bacteria such as Group A streptococci, which are an important human pathogen."

Ginsburg said that Hongmin Sun's achievement of constructing a transgenic mouse susceptible to streptococcus infection represents a major step not only in understanding infection by that bacterium, but in opening the way to similar studies of other bacteria.

In infecting its human host, the group A streptococcus secretes its own streptokinase, which activates the human form of the enzyme, plasminogen. Plasminogen, in turn, dissolves blood clots by degrading the protein, fibrin. A major question was what role streptokinase played in the bacterium's overall pathogenicit
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
26-Aug-2004


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