The IgG-binding domains contributed only when Sbi was attached to the cell, while only the secreted C3-binding domains were biologically active

The IgG-binding domains contributed only when Sbi was attached to the cell, while only the secreted C3-binding domains were biologically active. == INTRODUCTION == Staphylococcus aureuspermanently colonizes the moist squamous epithelium of the anterior nares of approximately 20% of the population (45). in the culture supernatant and is also associated with the cell envelope.S. aureusstrains that expressed truncates of Sbi lacking N-terminal domains D1 and D2 (D1D2) or D3 and D4 (D3D4) or a C-terminal truncate that was no Quinapril hydrochloride longer retained in the cell envelope were analyzed. Both the secreted and envelope-associated forms of Sbi contributed to immune evasion. The IgG-binding domains contributed only when Sbi was attached to the cell, while only the secreted C3-binding domains were biologically active. == INTRODUCTION == Staphylococcus aureuspermanently colonizes the moist squamous epithelium of the anterior nares of approximately 20% of the population (45). Colonization is an established risk factor Rabbit polyclonal to CD20.CD20 is a leukocyte surface antigen consisting of four transmembrane regions and cytoplasmic N- and C-termini. The cytoplasmic domain of CD20 contains multiple phosphorylation sites,leading to additional isoforms. CD20 is expressed primarily on B cells but has also been detected onboth normal and neoplastic T cells (2). CD20 functions as a calcium-permeable cation channel, andit is known to accelerate the G0 to G1 progression induced by IGF-1 (3). CD20 is activated by theIGF-1 receptor via the alpha subunits of the heterotrimeric G proteins (4). Activation of CD20significantly increases DNA synthesis and is thought to involve basic helix-loop-helix leucinezipper transcription factors (5,6) for the development of invasive disease in both the hospital and the community (27). Common community-acquired and nosocomialS. aureusinfections include superficial skin lesions such as boils, abscesses, and impetigo, while invasive infections include septic arthritis, pneumonia, osteomyelitis, and endocarditis (13). Quinapril hydrochloride The ability ofS. aureusto cause such a diverse range of infections is due in part to cell surface-associated proteins and extracellular toxins. Some cell surface-associated proteins bind to components of the extracellular matrix (ECM) of the host. These bacterial adhesins are called MSCRAMMs (microbialsurfacecomponentsrecognizingadhesivematrixmolecules). Others promote evasion of host innate immune responses (12). Protein A (Spa) was originally thought to be the only IgG-binding protein inS. aureus. Spa is a cell wall-anchored protein that consists of 4 or 5 5 homologous repeat domains of 56 to 61 residues that bind a variety of ligands, including IgG (Fig. 1) (30). A single Spa ligand-binding domain is composed of a three-helix bundle of antiparallel alpha-helices (7). The binding sites of the Fc region of IgG, von Willebrand factor, and tumor necrosis factor receptor-1 (TNFR-1) are located on helices 1 and 2, while the binding site of the VH3 element of IgM is on helices 2 and 3 (34). == Fig. 1. == Schematic diagrams of Spa and Sbi. The upper part of the figure shows Sbi and the lower shows Spa. S, signal sequence; D1 to D4 (I to IV), Sbi ligand-binding domains that have sequence similarity to IgG-binding domains of Spa (E, D, A, B, C); Wr and Xr, proline-rich C terminal domains; Y, C-terminal domain likely to be involved in membrane binding; LPXTG, wall anchoring motif; M, transmembrane domain. Phage display studies ofS. aureusstrain 8325-4 genomic DNA revealed a novel Ig-binding peptide that was later found to be part of Sbi (secondbinding protein ofimmunoglobulin) (46,47). At its N terminus are Quinapril hydrochloride two IgG-binding domains (D1 and D2 [D1D2]) with sequence similarity to the IgG-binding domains of Spa (Fig. 1). Next are two independently folded domains (D3 and D4 [D3D4]) that bind to complement factor C3 (40). The C-terminal region of Sbi comprises a proline-rich repeat domain and a C-terminal domain rich in tyrosine and threonine that is likely to be involved in attaching the protein to the cell envelope (47). Four surface components ofS. aureushave been shown to promote evasion of neutrophil-mediated phagocytosis. Spa is known to inhibit opsonophagocytosis by binding IgG by the Fc region, which prevents classical complement fixation and recognition by the neutrophil Fc receptor (12). Clumping factor A (ClfA) is a major fibrinogen-binding surface protein. It is found predominantly on cells from the stationary phase of growth. ClfA binds to the -chain of fibrinogen via its N-terminal A-domain (29).S. aureus clfAmutants are significantly attenuated in murine models for sepsis and arthritis (22) and in a rat endocarditis model (36). Virulence is likely to be increased by bacterial cells becoming coated with fibrinogen, which inhibits deposition of, or access to, opsonins (18). In addition, ClfA can capture and activate serum complement regulator factor I and convert C3b to iC3b and C3d, resulting in the loss of opsonin (5,17). This also prevents C3 convertase formation and terminal pathway activation (5). The majority of clinical isolates ofS. aureusproduce serotype 5 or serotype 8 capsular polysaccharide (Cap) (33). Capsule expression reduces the uptake of bacteria by neutrophils in the presence of normal serum opsonins (28,32). Although complement factors can accumulate on the cell wall surface beneath the polysaccharide layer, they are inaccessible to complement receptors on neutrophils. The iron-regulated surface determinant protein IsdH is part of a complex of proteins that are expressed only under iron-restricted conditions. They extract heme from hemoglobin and transport it into the cytoplasm (43).S. aureusisdHmutants are engulfed more rapidly by human neutrophils in the presence of serum opsonins, survive poorly in fresh whole human blood, and are less.