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Serum opacity factor promotes group A streptococcal epithelial cell invasion and virulence.
- Source :
-
Molecular microbiology [Mol Microbiol] 2006 Oct; Vol. 62 (1), pp. 15-25. Date of Electronic Publication: 2006 Aug 30. - Publication Year :
- 2006
-
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 cotranscribed in a two-gene operon with a gene encoding another fibronectin-binding protein, sfbX. We compared the ability of a SOF(+) wild-type 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 fibronectin-binding 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.
- Subjects :
- Animals
Bacterial Proteins genetics
Bacterial Proteins metabolism
Carrier Proteins genetics
Carrier Proteins metabolism
Cell Line, Tumor
Epithelial Cells cytology
Epithelial Cells microbiology
Fibronectins metabolism
Humans
Intracellular Signaling Peptides and Proteins
Male
Mice
Mutation genetics
Peptide Hydrolases genetics
Protein Binding
Streptococcus pyogenes genetics
Streptococcus pyogenes pathogenicity
Virulence genetics
Epithelial Cells metabolism
Peptide Hydrolases metabolism
Streptococcus pyogenes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0950-382X
- Volume :
- 62
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 16942605
- Full Text :
- https://doi.org/10.1111/j.1365-2958.2006.05337.x