Shr is a broad-spectrum surface receptor that contributes to adherence and virulence in group A streptococcus.
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 the hemoglobin-haptoglobin complex. We previously reported that Shr is found in association with whole GAS cells and in culture supernatant. Here, we demonstrate that cell-associated Shr could not be released from the bacteria by the muralytic enzyme mutanolysin and was instead 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 the extracellular matrix. 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. The inactivation of shr resulted in a 40% reduction in 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 being a new microbial surface component recognizing adhesive matrix molecules in GAS that mediates attachment to epithelial cells and contributes to the infection process.
Fisher
Morly
M
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100, Israel.
Huang
Ya-Shu
YS
Li
Xueru
X
McIver
Kevin S
KS
Toukoki
Chadia
C
Eichenbaum
Zehava
Z
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001422:Bacterial Adhesion / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000472:pathogenicity*; D015027:Zebrafish
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins