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Science 27 August 2004:
Vol. 305. no. 5688, pp. 1283 - 1286
DOI: 10.1126/science.1101245
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Reports

Plasminogen Is a Critical Host Pathogenicity Factor for Group A Streptococcal Infection

Hongmin Sun,1 Ulrika Ringdahl,6 Jonathon W. Homeister,2 William P. Fay,1 N. Cary Engleberg,1,3 Angela Y. Yang,4 Laura S. Rozek,1 Xixi Wang,1 Ulf Sjöbring,6 David Ginsburg1,4,5*

Group A streptococci, a common human pathogen, secrete streptokinase, which activates the host's blood clot–dissolving protein, plasminogen. Streptokinase is highly specific for human plasminogen, exhibiting little or no activity against other mammalian species, including mouse. Here, a transgene expressing human plasminogen markedly increased mortality in mice infected with streptococci, and this susceptibility was dependent on bacterial streptokinase expression. Thus, streptokinase is a key pathogenicity factor and the primary determinant of host species specificity for group A streptococcal infection. In addition, local fibrin clot formation may be implicated in host defense against microbial pathogens.

1 Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
2 Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
3 Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
4 Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
5 Howard Hughes Medical Institute, Ann Arbor, MI 48109, USA.
6 Department of Laboratory Medicine, Section for Microbiology, Immunology, and Glycobiology, Lund University, SE-221-84 Lund, Sweden.

* To whom correspondence should be addressed. E-mail: ginsburg{at}umich.edu

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