Allele substitution of the streptokinase gene reduces the nephritogenic capacity of group A streptococcal strain NZ131

To investigate the role of allelic variants of streptokinase in the pathoge nesis of acute poststreptococcal glomerulonephritis (APSGN), site-specific integration plasmids were constructed, which contained either the non-nephr itis-associated streptokinase gene (skc5) from the group C streptococcal st rain Streptococcus equisimilis H46A or the nephritis-associated streptokina se gene (ska1) from the group A streptococcal nephritogenic strain NZ131. T he plasmids were introduced by electroporation and homologous recombination into the chromosome of an isogenic derivative of strain NZ131, in which th e streptokinase gene had been deleted and which had thereby lost its nephri togenic capacity in a mouse model of APSGN. The introduction of a non-nephr itis-associated allelic variant of streptokinase did not rescue the nephrit ogenic capacity of the strain. The mutant and the wild-type strains produce d 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 st reptokinase in the pathogenesis of APSGN is related to the allelic variant of the protein.