Allele substitution of the streptokinase gene reduces the nephritogenic capacity of group A streptococcal strain NZ131. 2000

A Nordstrand, and W M McShan, and J J Ferretti, and S E Holm, and M Norgren
Department of Clinical Bacteriology, Umeâ University, S-901 85 Umeâ, Sweden. annika.nordstrand@climi.umu.se

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.

UI MeSH Term Description Entries
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D003176 Complement C3 A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase. C3 Complement,C3 Precursor,Complement 3,Complement C3 Precursor,Complement Component 3,Precursor-Complement 3,Pro-C3,Pro-Complement 3,C3 Precursor, Complement,C3, Complement,Complement, C3,Component 3, Complement,Precursor Complement 3,Precursor, C3,Precursor, Complement C3,Pro C3,Pro Complement 3
D005921 Glomerulonephritis Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY. Bright Disease,Kidney Scarring,Glomerulonephritides,Scarring, Kidney
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013290 Streptococcal Infections Infections with bacteria of the genus STREPTOCOCCUS. Group A Strep Infection,Group A Streptococcal Infection,Group A Streptococcal Infections,Group B Strep Infection,Group B Streptococcal Infection,Group B Streptococcal Infections,Infections, Streptococcal,Infection, Streptococcal,Streptococcal Infection
D013297 Streptococcus pyogenes A species of gram-positive, coccoid bacteria isolated from skin lesions, blood, inflammatory exudates, and the upper respiratory tract of humans. It is a group A hemolytic Streptococcus that can cause SCARLET FEVER and RHEUMATIC FEVER. Flesh-Eating Bacteria,Streptococcus Group A,Bacteria, Flesh-Eating
D013300 Streptokinase Streptococcal fibrinolysin . An enzyme produced by hemolytic streptococci. It hydrolyzes amide linkages and serves as an activator of plasminogen. It is used in thrombolytic therapy and is used also in mixtures with streptodornase (STREPTODORNASE AND STREPTOKINASE). EC 3.4.-. Avelizin,Awelysin,Celiase,Distreptase,Kabikinase,Kabivitrum,Streptase,Streptodecase

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