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Infect. Immun. doi:10.1128/IAI.00300-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Shr is a broad-spectrum surface receptor that contributes to adherence and virulence in GAS

The Israel Institute for Biological Research, Department of Infectious Diseases, P.O. Box 19, Ness-Ziona, 74100, Israel; Georgia State University, Biology Department, P.O. Box 4010, Atlanta, GA 30302-4010; University of Maryland, Dept. of Cell Biology & Molecular Genetics and Maryland Pathogen Research Institute, College Park, MD 20742

^* To whom correspondence should be addressed. Email: zeichen{at}gsu.edu.

	Abstract

Group A streptococcus (GAS) is a common hemolytic pathogen that produces a range of suppurative infections and autoimmune sequelae in humans. Shr is an exported protein in GAS, which binds in vitro to hemoglobin, myoglobin, and hemoglobin-haptoglobin complex. We previously reported that Shr is found in association with whole GAS cells and in the culture supernatant. Here we demonstrate that the cell-associated Shr could not be released from the bacteria by the muralytic enzyme mutanolysin and instead was localized to the membrane. Shr was available, however, on the exterior of GAS, exposed to the extracellular environment. In vitro binding and competition assays demonstrated that in addition to hemoprotein binding, purified Shr specifically interacts with immobilized fibronectin and laminin. The absence of typical fibronectin-binding motifs indicates that a new protein pattern is involved in the binding of Shr to ECM. Recombinant Lactococcus lactis cells expressing Shr on the bacterial surface gained the ability to bind to immobilized fibronectin, suggesting that Shr can function as an adhesin. Inactivation of shr resulted in a 40% reduction of the attachment to human epithelial cells in comparison to the parent strain. GAS infection elicited a high titer of Shr antibodies in sera from convalescent mice, demonstrating that Shr is expressed in vivo. The shr mutant was attenuated for virulence in an intramuscular zebrafish model system. In summary, this study identifies Shr as a new MASCRAMM in GAS that mediates attachment to epithelial cells and contributes to the infection process.