Identification of an extracellular plasmin binding protein from nephritogenic streptococci.

Abstract

SummaryExamination of the extracellular products of nephritis(+) and nephritis(-) group A streptococci revealed the presence of a 46-kD protein secreted by nephritogenic strains that binds to human plasmin. Immunological data revealed that this protein, called nephritis plasmin binding protein (NPBP), is not related to group A streptokinase nor to a recently described streptococcal dehydrogenase protein. The binding of human plasmin to this protein can be blocked by e-amino caproic acid, indicating the importance of lysine groups in the binding process. Mutanolysin extracts of cell walls from these nephritogenic strains probed with anti-NPBP antibody were negative for cell wall-bound NPBP. Serological data with acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever sera indicated that the protein reacts preferentially with APSGN sera. Amino acid sequence analysis and immunological reactivity suggest NPBP is the streptococcal pyrogenic exotoxin B precursor, also previously described as zymogen (streptococcal proteinase precursor). The secretion of both group A streptokinase and a secreted plasmin binding protein in the same nephritogenic strain raises an intriguing hypothesis of the mechanism of action of this protein in APSGN.

The Current State of Poststreptococcal Glomerulonephritis

“…3 Two antigens are actively investigated at the present time as the potential cause(s) of PSGN: The nephritis-associated plasmin receptor (NAPlr), identified as glyceraldehyde-3-phosphate dehydrogenase, 59,60 and a cationic cysteine proteinase known as streptococcal pyrogenic exotoxin B (SPEB) that is generated by proteolysis of a zymogen precursor (zSPEB). [61][62][63] Both of these fractions are capable of activating the alternate pathway of the complement system. 3 NAPlr deposits are present in early biopsies of acute PSGN, and NAPlr antibody levels are detected by Western blot in convalescent sera of 92% of the patients with PSGN and 60% of uncomplicated streptococcal infections in Japan.…”

Clonal diversity ofStreptococcus pyogeneswithin some M-types revealed by multilocus enzyme electrophoresis

“…However, some outbreaks of a 'nephritogenic' M-type infection do not result in APSGN. The rarity of repeat attacks of APSGN suggests that a first attack is sufficient to induce immunity to all nephritogenic strains and that disease induction depends on one or more molecules common to all such nephritogenic strains; several candidate molecules have been identified [16][17][18][19].…”

Insights from Genomics on Post-Infectious Streptococcal Glomerulonephritis

“…Zabriskie and co-workers first observed that strains were associated with APSGN produced an extracellular protein not seen in non-nephritis strains, which was subsequently found to be bound to plasmin (Poon-King et al, 1993;Villarreal et al, 1979). This plasmin binding protein was discovered to be the major extracellular protease SpeB, and analysis of patient sera showed significantly higher levers of anti-SpeB antibodies in APSGN patients as compared to rheumatic fever patients or controls (Cu et al, 1998;Poon-King et al, 1993).…”