Serum opacity factor promotes group A streptococcal epithelial cell invasion and virulence

Authors

A M. Timmer, University of California, San Diego, USA
S. A. Kristian, University of California, San Diego, USA
V. Datta, University of California, San Diego, USA
A. Jeng, University of California, San Diego, USA
C. M. Gillen, University of WollongongFollow
Mark J. Walker, University of WollongongFollow
B. Beall, Center for Disease Control and Prevention, Atlanta, USA
V. Nizet, University of California, San Diego, USA

RIS ID

17276

Publication Details

This article was originally published as Timmer, AM, Kristian, SA, Datta, V, Jeng, A, Gillen, CM, Walker, MJ, Beall, B and Nizet, V, Serum opacity factor promotes group A streptococcal epithelial cell invasion and virulence, Molecular Microbiology 62, 15-25, 2006. Copyright 2006 Blackwell Publishing. The definitive version is available at www.blackwell-synergy.com.

Abstract

Serum opacity factor (SOF) is a bifunctional cell surface protein expressed by 40-50% of group A streptococcal (GAS) strains comprised of a C-terminal domain that binds fibronectin and an N-terminal domain that mediates opacification of mammalian sera. The sof gene was recently discovered to be co-transcribed in a two-gene operon with a gene encoding another fibronectin-binding protein, sfbX. We compared the ability of a SOF(+) wild-type (WT) serotype M49 GAS strain and isogenic mutants lacking SOF or SfbX to invade cultured HEp-2 human pharyngeal epithelial cells. Elimination of SOF led to a significant decrease in HEp-2 intracellular invasion while loss of SfbX had minimal effect. The hypoinvasive phenotype of the SOF(-) mutant could be restored upon complementation with the sof gene on a plasmid vector, and heterologous expression of sof49 in M1 GAS or Lactococcus lactis conferred marked increases in HEp-2 cell invasion. Studies using a mutant sof49 gene lacking the fibronectinbinding domain indicated that the N-terminal opacification domain of SOF contributes to HEp-2 invasion independent of the C-terminal fibronectin binding domain, findings corroborated by observations that a purified SOF N-terminal peptide could promote latex bead adherence to HEp- 2 cells and inhibit GAS invasion of HEp-2 cells in a dose-dependent manner. Finally, the first in vivo studies to employ a single gene allelic replacement mutant of SOF demonstrate that this protein contributes to GAS virulence in a murine model of necrotizing skin infection.