Spa Contributes to the Virulence of Type 18 Group A Streptococci

McLellan, Duncan; Chiang, Edna Y.; Courtney, Harry S.; Hasty, David L.; Wei, Shirley C.; Hu, Mary C.; Walls, Michael A.; Bloom, Jackie J.; Dale, James B.

doi:10.1128/iai.69.5.2943-2949.2001

Cited by 30 publications

(24 citation statements)

References 25 publications

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“…These included SzM of S. equi subsp. zooepidemicus, Spa of S. pyogenes strain 18 and DemA/B of Streptococcus dysgalactiae, as noted elsewhere (Dale et al, 1999;Kelly et al, 2006;McLellan et al, 2001;Vasi et al, 2000). Others included (A repeats of) the Mrp/FcrA protein family of S. pyogenes and (repeated residues in) Sez 1778 of S. zooepidemicus strain MGCS10565 (Beres et al, 2008;O'Toole et al, 1992).…”

Section: Resultsmentioning

confidence: 95%

“…5 (Heath et al, 1990;Vasi et al, 2000). Although the ligand-binding properties of SzM, Spa and Sez 1778 are unknown (Beres et al, 2008;Dale et al, 1999;McLellan et al, 2001), it seems highly likely that Spa and SzM are capable of binding IgG given the virtual identity of their Cterminal domains to residues 255-534 of FgBP (95 and 98 % identity, respectively; Dale et al, 1999;Kelly et al, 2006;McLellan et al, 2001) and that this accounts for the reported anti-phagocytic properties of Spa (Dale et al, 1999).…”

Section: Resultsmentioning

confidence: 99%

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Localization of the equine IgG-binding domain in the fibrinogen-binding protein (FgBP) of Streptococcus equi subsp. equi

et al. 2009

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Fibrinogen-binding protein (FgBP, also termed SeM) is a cell-wall-associated anti-phagocytic M-like protein of the equine pathogen Streptococcus equi subsp. equi, and binds fibrinogen (Fg) and IgG. FgBP binds Fg avidly through residues located at the extreme N terminus of the molecule, whereas the IgG-binding site is more centrally located between the A and B repeats. FgBP binds equine IgG4 and IgG7 subclasses through interaction with the CH2–CH3 interdomain region of IgG-Fc, and possesses overlapping Fc-binding sites with protein A and protein G. In this study, FgBP truncates containing defined internal deletions were used to identify a stretch of 14 aa (residues 335–348) critical for IgG binding. Protein chimeras consisting of the non-IgG-binding α-helical coiled-coil M5 protein fused to FgBP sequences were used to identify a minimal equine IgG-binding domain consisting of residues 329–360. Competition ELISA tests suggested that IgG does not compromise Fg binding and vice versa.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Localization of the equine IgG-binding domain in the fibrinogen-binding protein (FgBP) of Streptococcus equi subsp. equi

et al. 2009

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“…Many of the GAS surface proteins that we did not test also possess an LPXTG motif followed by an acidic amino acid, which makes it likely that they require SrtA as well. These include serum opacity factor (12), streptococcal protective antigen (41), and the collagen-like protein Scl1 (34), all of which have been shown in one or more model systems to have possible roles in GAS pathogenesis. The role of SrtB in virulence is less clear.…”

Section: Discussionmentioning

confidence: 99%

Differential Recognition of Surface Proteins inStreptococcus pyogenesby Two Sortase Gene Homologs

2002

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The interaction of Streptococcus pyogenes (group A streptococcus [GAS]) with its human host requires several surface proteins. In this study, we isolated mutations in a gene required for the surface localization of protein F by transposon mutagenesis of the M6 strain JRS4. This gene (srtA) encodes a protein homologous to Staphylococcus aureus sortase, which covalently links proteins containing an LPXTG motif to the cell wall. The GAS srtA mutant was defective in anchoring the LPXTG-containing proteins M6, protein F, ScpA, and GRAB to the cell surface. This phenotype was complemented when a wild-type srtA gene was provided in trans. The surface localization of T6, however, was unaffected by the srtA mutation. The M1 genome sequence contains a second open reading frame with a motif characteristic of sortase proteins. Inactivation of this gene (designated srtB) in strain JRS4 affected the surface localization of T6 but not M6, protein F, ScpA, or GRAB. This phenotype was complemented by srtB in trans. An srtA probe hybridized with DNA from all GAS strains tested (M types 1, 3, 4, 5, 6, 18, 22, and 50 and nontypeable strain 64/14) and from streptococcal groups C and G, while srtB hybridized with DNA from only a few GAS strains. We conclude that srtA and srtB encode sortase enzymes required for anchoring different subsets of proteins to the cell wall. It seems likely that the multiple sortase homologs in the genomes of other gram-positive bacteria have a similar substrate-specific role.Streptococcus pyogenes (group A streptococcus [GAS]) is a gram-positive pathogen capable of causing a wide variety of diseases (13). The majority of these are mild, suppurative infections, including pharyngitis and pyoderma, which are sometimes followed by serious sequelae such as rheumatic fever, acute glomerulonephritis, and reactive arthritis. More recently, this organism has become notorious for its ability to cause severe invasive diseases with high mortality rates. These include streptococcal toxic shock syndrome, septicemia, and the "flesh-eating" disease necrotizing fasciitis. The pathogenesis of GAS infections is attributed to the ability of these organisms to produce a wide array of virulence factors, including secreted toxins and superantigens, which are responsible for many of the symptoms characteristic of GAS disease and cell-associated molecules that are used to adhere to and interact with the host.Surface proteins of gram-positive bacteria are attached to the cell surface by one of several mechanisms (11). Some surface proteins are noncovalently attached to teichoic and lipoteichoic acids, anchored directly to the cytoplasmic membrane, or covalently attached to the cell wall cross-bridge. In GAS, many surface proteins appear to be covalently anchored to the cell wall, although others, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and ␣-enolase, are anchored by an as yet unidentified mechanism. Covalent attachment of proteins to the cell wall cross-bridge is catalyzed by the enzyme sortase, whose mechanism of ...

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“…A third M-type specific loci, Spa, also contains a number of adhesin genes. Although the function of Spa itself remains unknown Spa-deficient mutant were shown to have an impaired virulence in mouse models (McLellan, et al, 2001). …”

Section: Comparative Genomicsmentioning

confidence: 99%