, 2005) and mediate GAS adherence to and internalization by human cells (Caswell et al., 2007). The amino-terminal part of the

Scl proteins, termed the variable (V) region, forms a globular domain that is protruded away from the GAS cell surface by the CL region (Xu et al., 2002). The V-region sequences vary significantly between Scl1 and Scl2. In addition, the V-region sequence of each Scl protein is conserved in strains of the same M-type, but differs considerably among Scls from strains of different M-types. Despite the observed sequence variation, LY2157299 two main ligands have been identified that bind different Scl1 variants via their V-regions. The Scl1.6 and Scl1.55 proteins of M6- and M55-type GAS, respectively, bind human plasma glycoproteins factor H and the factor H-related protein 1 (Caswell et al., 2008b). On the contrary, several other Scl1 variants bind the low-density lipoprotein (LDL) including Scl1 proteins

of the M1-, M2-, M12-, M28-, and M41-type GAS (Han et al., 2006a). The latter Scl1.41 protein also binds integrins α2β1 and α11β1 via direct interaction with the CL region (Caswell et al., 2008a). This suggests specialization in ligand binding among Scl1 proteins and underscores their importance as pathogenicity traits. The binding of the ECM components by pathogens is known to be a common strategy used to establish host colonization. Several GAS cell-surface molecules Selleckchem GW-572016 have been reported to initiate this interaction Megestrol Acetate including several M proteins, F1/SfbI, F2, SOF, SfbII, Lbp, and Shr (Hanski & Caparon, 1992; Kreikemeyer et al., 1995; Jaffe et al., 1996; Molinari & Chhatwal, 1998; Courtney et al., 1999; Terao et al., 2002; Fisher et al., 2008). Thus, in this work, we hypothesized that Scl proteins possess binding capacities to ECM components that, in turn, would facilitate bacterial adhesion to human ECM and internalization by host cells. It is known that Scl1 is expressed by virtually all GAS strains (Lukomski et al., 2000; Rasmussen et al., 2000); therefore, this

work further supports the role of Scl1 protein as an important accessory, multifunctional surface adhesin of GAS. The M41-type MGAS 6183 wild type and the scl1 mutant strains were used. The isogenic scl1 mutant of MGAS 6183 was constructed by allelic replacement as described previously (Caswell et al., 2007). To prepare GAS cells for experiments, cultures were grown overnight on brain–heart infusion agar (BD Biosciences, Sparks, MD) at 37 °C in an atmosphere of 5% CO2–20% O2. Overnight cultures were used to inoculate Todd–Hewitt broth (BD Biosciences) supplemented with 0.2% yeast extract and the cultures were incubated at 37 °C until they reached the logarithmic phase of growth (OD600 nm∼0.5).