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A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen
Theresa O. Harris, … , John F. Bohnsack, Craig E. Rubens
Theresa O. Harris, … , John F. Bohnsack, Craig E. Rubens
Published January 1, 2003
Citation Information: J Clin Invest. 2003;111(1):61-70. https://doi.org/10.1172/JCI16270.
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Article Virology Article has an altmetric score of 6

A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen

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Abstract

Group B streptococcus (GBS) is an important human pathogen. In this study, we sought to identify mechanisms that may protect GBS from host defenses in addition to its capsular polysaccharide. A gene encoding a cell-surface–associated protein (cspA) was characterized from a highly virulent type III GBS isolate, COH1. Its sequence indicated that it is a subtilisin-like extracellular serine protease homologous to streptococcal C5a peptidases and caseinases of lactic acid bacteria. The wild-type strain cleaved the α chain of human fibrinogen, whereas a cspA mutant, TOH121, was unable to cleave fibrinogen. We observed aggregated material when COH1 was incubated with fibrinogen but not when the mutant strain was treated similarly. This suggested that the product(s) of fibrinogen cleavage have strong adhesive properties and may be similar to fibrin. The cspA gene was present among representative clinical isolates from all nine capsular serotypes, as revealed by Southern blotting. A cspA– mutant was ten times less virulent in a neonatal rat sepsis model of GBS infections, as measured by LD50 analysis. In addition, the cspA– mutant was significantly more sensitive than the wild-type strain to opsonophagocytic killing by human neutrophils in vitro. Taken together, the results suggest that cleavage of fibrinogen by CspA may increase the lethality of GBS infection, potentially by protecting the bacterium from opsonophagocytic killing.

Authors

Theresa O. Harris, Daniel W. Shelver, John F. Bohnsack, Craig E. Rubens

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Figure 3

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Western blot analysis of CspA expression in E. coli and GBS strains usin...
Western blot analysis of CspA expression in E. coli and GBS strains using anti-CspA sera. Lane 1 shows periplasmic extract from E. coli DH5α containing pBS (negative control); Lane 2 shows periplasmic extract from E. coli DH5α containing pTH5 (XbaI fragment bearing cspA in pBSKS–; Stratagene). Note that that the lower migration of CspA in periplasmic extracts is due to a mutation in pTH5 that prematurely terminates translation (see Methods). Lanes 3–6 show mutanolysin-extracted GBS surface proteins from COH1 (lane 3), TOH121 (cspA–, lane 4), TOH97 (scpB–, lane 5), and TOH144 (cspA–, scpB–, lane 6). Migration of molecular mass markers (in kDa) is indicated on the left.

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