Opacity factor activity and epithelial cell binding by the serum opacity factor protein of Streptococcus pyogenes are functionally discrete

The Journal of Biological Chemistry
Christine M GillenMark J Walker

Abstract

Serum opacity factor (SOF) is a unique multifunctional virulence determinant expressed at the surface of Streptococcus pyogenes and has been shown to elicit protective immunity against GAS infection in a murine challenge model. SOF consists of two distinct domains with different binding capacities: an N-terminal domain that binds apolipoprotein AI and a C-terminal repeat domain that binds fibronectin and fibrinogen. The capacity of SOF to opacify serum by disrupting the structure of high density lipoproteins may preclude its use as a vaccine antigen in humans. This study generated mutant forms of recombinant SOF with reduced (100-fold) or abrogated opacity factor (OF) activity, for use as vaccine antigens. However, alterations introduced into the N-terminal SOF peptide (SOFDeltaFn) by mutagenesis to abrogate OF activity, abolish the capacity of SOF to protect against lethal systemic S. pyogenes challenge in a murine model. Mutant forms of purified SOFDeltaFn peptide were also used to assess the contribution of OF activity to the pathogenic processes of cell adhesion and cell invasion. Using latex beads coated with full-length SOF, SOFDeltaFn peptide, or a peptide encompassing the C-terminal repeats (FnBD), we demonstrate that a...Continue Reading

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Citations

Mar 12, 2009·The Journal of Biological Chemistry·Harry S CourtneyW Scott Argraves
May 29, 2012·Journal of Bacteriology·Srivishnupriya AnbalaganMichael S Chaussee
Feb 3, 2012·Annals of Clinical Microbiology and Antimicrobials·Thangarajan Durai AnandParamasamy Gunasekaran
Apr 1, 2010·Future Microbiology·Debra E Bessen, Sergio Lizano
Sep 10, 2009·Annual Review of Pathology·Randall J Olsen, James M Musser
Jun 18, 2016·FEBS Letters·Stephan BrouwerMark J Walker
Jun 18, 2014·Infection and Immunity·Alaullah SheikhJames M Fleckenstein
Apr 4, 2014·Clinical Microbiology Reviews·Mark J WalkerVictor Nizet

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