title: Streptococcal protein FOG, a novel matrix adhesin interacting with collagen I in vivo.
abstract: Group G streptococcus (GGS) is a human pathogen of emerging clinical significance. It causes skin and soft tissue infections, occasionally resulting in life-threatening conditions such as sepsis and necrotizing fasciitis. We recently identified FOG, a novel surface protein of GGS with fibrinogen binding and immune evasion properties. Here we investigated the role of FOG in streptococcal primary adhesion to host tissue. A FOG-expressing clinical isolate adhered more efficiently to human skin biopsies ex vivo and to the murine dermis in vivo than a FOG-deficient strain. Scanning and transmission electron microscopy of skin specimens exhibited that this property was assigned to the ability of FOG to interact with collagen I, a major interstitial component of the dermis. Overlay experiments with human skin extracts and radiolabeled FOG followed by matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis identified both the alpha1- and alpha2-chains of collagen I as targets for FOG. Transmission electron microscopy of the molecular complexes revealed thread-like FOG molecules binding via their NH2 termini to distinct sites on collagen I monomers and fibrils. The results demonstrate that FOG is important for GGS adhesion in vivo, implying a pathogenic role for this surface protein.
authors.affiliation: Department of Clinical Sciences, Section for Clinical and Experimental Infectious Medicine, Biomedical Center, Lund University, S-22184 Lund, Sweden.
authors.forename: D Patric
authors.initials: DP
authors.lastname: Nitsche
authors.forename: Helena M
authors.initials: HM
authors.lastname: Johansson
authors.forename: Inga-Maria
authors.initials: IM
authors.lastname: Frick
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D003094:Collagen / Q000378:metabolism*; D020405:Dermis / Q000382:microbiology / Q000473:pathology; D006801:Humans; D011485:Protein Binding; D012867:Skin / Q000382:microbiology / Q000473:pathology; D013291:Streptococcus / Q000302:isolation & purification / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D003094:Collagen