Polymorphism of the streptokinase gene: implications for the pathogenesis of post-streptococcal glomerulonephritis

Recent studies of streptokinase genes from epidemiologically and clinically defined streptococci of groups A, C and G have provided evidence of the polymorphism of the streptokinase locus in the chromosome of pathogenic streptococci. This review considers genetic and pathogenetic data suggesting that there exists a causal relationship between nephritis strain-associated streptokinase production and the initial stages of post-streptococcal glomerulonephritis (PSGN). Currently available sequence information allows to recognize, in the middle of the streptokinase molecule, a major variable region, V1, of about 70 amino acid residues in which sequence identity drops to below 50% when the proteins from nephritogenic and non-nephritogenic strains are compared. The V1 regions, although showing microheterogeneity within either protein category, appear to be more hydrophobic and possess a higher content of ordered secondary structures in the "nephritogenic" molecules. As a working hypothesis, they may be considered the nephrotropic domain(s) with which streptokinases from nephritogenic strains bind to glomerular structures and activate plasminogen in situ, thus triggering the cascade of proteolytic processes leading to PSGN.