Identification and Characterization of a Novel Secreted Immunoglobulin Binding Protein from Group A Streptococcus

Abstract

Immunoglobulin binding proteins are one of several pathogenicity factors which have been associated with invasive disease caused by group A streptococci. The surface-bound M and M-like proteins of Streptococcus pyogenes are the most characterized of these immunoglobulin binding proteins, and in most cases they bind only a single antibody class. Here we report the identification of a novel non-M-type secreted protein, designated SibA (for secreted immunoglobulin binding protein from group A streptococcus), which binds all immunoglobulin G (IgG) subclasses, the Fc and Fab fragments, and also IgA and IgM. SibA has no significant sequence homology to any M-related proteins, is not found in the vir regulon, and contains none of the characteristic M-protein regions, such as the A or C repeats. Like M proteins, however, SibA does have relatively high levels of alanine, lysine, glutamic acid, leucine, and glycine. SibA and M proteins also share an alpha-helical N-terminal secondary structure which has been previously implicated in immunoglobulin binding in M proteins. Evidence presented here indicates that this is also the case for SibA. SibA also has regions of local similarity with other coiled-coil proteins such as Listeria monocytogenes P45 autolysin, human myosin heavy chain, macrogolgin, and Schistoma mansoni paramyosin, some of which are of potential significance since cross-reactive antibodies between myosin proteins and M proteins have been implicated in the development of the autoimmune sequelae of streptococcal disease.The resurgence of severe group A streptococcal (GAS) disease has led to increased research efforts into the pathogenicity mechanisms of the causal bacterial species, Streptococcus pyogenes. This agent is responsible for a wide variety of diseases, ranging from uncomplicated pharyngitis (5) and impetigo (14) to severe life-threatening invasive conditions such as toxic shock-like syndrome, necrotizing fasciitis, and scarlet fever (30,31). Complications of GAS infections can also lead to the poststreptococcal sequelae of rheumatic fever and glomerulonephritis (32). The exact mechanisms of GAS pathogenesis have not yet been fully elucidated; however, it has been demonstrated that these bacteria are capable of interacting with a large number of host cells and tissues types. This diversity has led to the speculation that the type of colonization event, e.g., adhesion and at times internalization, contributes directly to the various manifestations of disease (for reviews, see references 11, 12, and 21).Immunoglobulin binding proteins are one of the pathogenicity factors which have been associated with invasive GAS disease (4, 23). The mechanism of their action is not fully understood; however, it is likely that they contribute to evasion of the host's immune defenses. Binding of both immunoglobulin A (IgA) and IgG or of IgG alone is found in all invasivedisease clinical isolates (24), whereas in septicemia and noninvasive throat strains, immunoglobulin binding is not a common characteristic (28). Near...

Is the GehD Lipase from Staphylococcus epidermidis a Collagen Binding Adhesin?

“…Deconvolution of the mature GehD data using the SELCON and VARSLC1 programs revealed that the predicted overall secondary structure of mature GehD consists of ϳ26.5% ␣-helix, 20.6% ␤-sheet, and 52.9% coil. This secondary structure composition differs markedly from that of the reported crystal structure of Cna-(151-318): 8% ␣-helix, 53% ␤-sheet, and 39% coil (29). …”

“…Additional proteins with adhesive functions located on the surface without LPXTG motifs include SEN (27), a surface enolase of S. pyogenes, SDH (28), a surface dehydrogenase of group A streptococci, and the S. epidermidis autolysin AtlE, which specifically binds to vitronectin (11). Anchorless proteins with other biological functions have also been described (29,30). Clearly, the number of anchorless adhesins identified in Gram-positive bacteria will increase in the future, but it is not clear if these proteins are virulence factors.…”

Streptococcus pyogenes Ser/Thr Kinase-regulated Cell Wall Hydrolase Is a Cell Division Plane-recognizing and Chain-forming Virulence Factor

“…1) and thus established a direct link between SP-STK and CdhA. Earlier, CdhA/SPy0019 was identified as SibA because of its ability to bind to human immunoglobulin (18). However, apart from this function, the physiologically relevant role of this protein in GAS has not been described.…”

“…CdhA Does Not Contribute Significantly to the Overall GAS Ability to Bind hIgGs-SPy0019 is a secretory protein and was previously termed as SibA based on its ability to bind hIgG (hence named SibA) (18). Fluorescence microscopy with antiSPy0019 antibody indicated that SPy0019/SibA is located both at the septum and on the surface.…”

“…In GAS, PscB ortholog is SPy0019, a secreted protein of unknown function. The purified SPy0019 has been previously reported to possess a human immunoglobulin binding ability and hence was termed as SibA (immunoglobulin-binding protein of group A Streptococcus) (18). Besides pneumococcal and group B streptococcal PcsB (15)(16)(17), SPy0019 is structurally similar to Streptococcal mutans GbpB/SagA (19), Streptococcus thermophilus Cse (20), Enterococcus faecalis/faecium (SalB/SagA) (21,22), and Listeria monocytogenes p45 protein (23).…”