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Infection and Immunity, March 2000, p. 1019-1025, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Allele Substitution of the Streptokinase Gene Reduces the Nephritogenic Capacity of Group A Streptococcal Strain NZ131

Annika Nordstrand,1,* W. Michael McShan,2 Joseph J. Ferretti,2 Stig E. Holm,1 and Mari Norgren1

Department of Clinical Bacteriology, Umeå University, S-901 85 Umeå, Sweden,1 and Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731902

Received 18 June 1999/Returned for modification 24 September 1999/Accepted 23 November 1999

To investigate the role of allelic variants of streptokinase in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), site-specific integration plasmids were constructed, which contained either the non-nephritis-associated streptokinase gene (skc5) from the group C streptococcal strain Streptococcus equisimilis H46A or the nephritis-associated streptokinase gene (ska1) from the group A streptococcal nephritogenic strain NZ131. The plasmids were introduced by electroporation and homologous recombination into the chromosome of an isogenic derivative of strain NZ131, in which the streptokinase gene had been deleted and which had thereby lost its nephritogenic capacity in a mouse model of APSGN. The introduction of a non-nephritis-associated allelic variant of streptokinase did not rescue the nephritogenic capacity of the strain. The mutant and the wild-type strains produced equivalent amounts of streptokinase. Complementation of the ska deletion derivative with the original ska allele reconstituted the nephritogenicity of wild-type NZ131. The findings support the hypothesis that the role of streptokinase in the pathogenesis of APSGN is related to the allelic variant of the protein.


* Corresponding author. Mailing address: Department of Clinical Bacteriology, Umeå University, S-90185 Umeå, Sweden. Phone: 46 90 7851121. Fax: 46 90 7852225. E-mail: annika.nordstrand{at}climi.umu.se.


Infection and Immunity, March 2000, p. 1019-1025, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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