Insights from Genomics on Post-Infectious Streptococcal Glomerulonephritis

Abstract

Acute post-streptococcal glomerulonephritis (APSGN) is one of the nonsuppurative sequelae that can occur following a group A streptococcal infection, the other common postinfection sequelae being rheumatic heart disease. Worldwide, it is estimated that approximately 470,000 cases of APSGN occur annually. Children and young adults most commonly are affected with males having twice the incidence as females. By the middle of the twentieth century, evidence was found that streptococcal skin infections were associated with APSGN, and these infections usually did not cause rheumatic fever, leading to the hypothesis that certain GAS strains were “rheumatogenic” while others were “nephritogenic.” In contrast to the molecular and immunological details that have brought considerable insight into the pathogenesis of rheumatic heart disease, the bacterial and host factors that contribute to ASPGN remain poorly defined and at times controversial. Modern bacterial genome sequencing projects have now provided a rich genetic resource that includes complete sequences of nephritogenic group A streptococcus strain NZ131 (McShan et al., 2008) and nephritogenic group C streptococcus strain MGCS10565 (Beres et al., 2008) as well as other group A and C strains associated with rheumatic heart disease and other syndromes. A metagenomic analysis is presented and considers the contribution of genes previously associated with APSGN strains (such as streptokinase, protease SpeB, and M protein) as well as other potential genetic factors that may be found uniquely in these genomes including genes acquired by horizontal transfer and via mobile genetic elements. This analysis provides complementary information to the many published studies using nephritogenic S. pyogenes strain NZ131 and places them in a broader context, shedding light upon the genetic basis for the human disease caused by this and related streptococci.