Fibrinogen binding and resistance to phagocytosis of Streptococcus sanguis expressing cloned M protein of Streptococcus pyogenes

Poirier, T.; Kehoe, Michael; Whitnack, E; Dockter, Michael E.; Beachey, Edwin H.

doi:10.1128/iai.57.1.29-35.1989

Cited by 43 publications

(17 citation statements)

References 19 publications

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“…However, the response of PLN cells from rM5-immunized mice to sM5[300-3191 was not detectable, as shown previously, whereas sM5 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] induced significant responses, as achieved previously with the longer peptide M5[1-35] (28).…”

Section: Resultssupporting

confidence: 61%

“…Groups of BALB/c mice were immunized with synthetic peptides in FCA and boosted with the same peptide in FIA to determine whether T-cell recognition sites within the peptide could provide help for anti-peptide antibody responses. IgG was measured by ELISA in sera from individual mice immunized with sM5[300-319], sM5 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], or rM5 ( Fig. 6).…”

Section: Resultsmentioning

confidence: 99%

“…M proteins are one of the major virulence factors expressed by Streptococcus pyogenes, as well as being the principal protective antigens recognized by the host (9,15,29). They form fibrillar a-helical coiled-coil dimers protruding from the surface of group A streptococci which mediate resistance to phagocytosis through their ability to bind mammalian proteins, including fibrinogen (26) and complement factor H (14), preventing effective opsonization by the alternative complement pathway. Sequence variability in the protruding amino-terminal halves of the molecules defines multiple M types, but the carboxy-terminal halves, which are located closer to the cell surface, are highly conserved between M types.…”

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confidence: 99%

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Characterization of a conserved helper-T-cell epitope from group A Streptococcal M proteins

1993

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We have previously defined major histocompatibility complex (MHC) class II-restricted T-cell epitopes from the carboxy-terminal region of group A streptococcal type 5 M protein. In this report, T-cell responses to one of these epitopes have been characterized in detail. T-cell clones from recombinant M5-immunized mice and popliteal lymph node cells from peptide-immunized mice were used to show that sM5[300-3191 is recognized in the context of I-A alleles of four of nine independent MHC class II haplotypes: I-Ad, I-Af, I-Ak, and I-AS. This epitope was also recognized by both helper (Th2) and inflammatory (Thl) subsets of murine T cells. The I-Ad-restricted epitope recognized by BALB/c mice was mapped to the 12-amino-acid peptide sM5[308-3191 and was shown to provide helper function for an immunoglobulin G anti-peptide antibody response in BALB/c mice. Anti-peptide antibody was shown to be specific for M5[304-3151 but failed to recognize intact rM5, suggesting that the conformation of the epitope differed between peptide and protein. However, the results demonstrate that overlapping epitopes can be the focus for both immunoglobulin G antibodies and the T cells which augment their production. Comparison of the available sequences for M proteins indicated that the T-cell epitope within M5[300-319] was highly conserved between M types and hence may elicit helper function for protective antibody responses to a wide range of M types. T-cell epitopes from conserved regions of M proteins which are recognized in the context of multiple MHC haplotypes have potential for the design of multivalent streptococcal vaccines.

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Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Characterization of a conserved helper-T-cell epitope from group A Streptococcal M proteins

1993

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“…The M protein has been postulated as the major virulence factor of group A streptococci primarily because of its association with phagocytosis-resistant phenotype. Molecular evidence for this hypothesis relied on analysis of GAS strains or serotypes which carried a single emm gene and no emm-related genes on their genomes (Norg-ren et al, 1989;Poirier et al, 1989). However, many GAS serotypes exhibit a different genome organization, with one containing not only an emm gene but also genes coding for structurally similar M-related proteins (Podbielski, 1993;Hollingshead et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Compared to the wild-type strains, isogenic GAS mutants having lost their ability to express serotypes 6 or 24 M proteins, were found to be sensitive to phagocytosis (Norgren et al, 1989;Courtney et al, 1994). Expression of recombinant serotypes 5 or 6 M proteins in Streptococcus gordonii or M 7 isogenic mutants, respectively, conferred resistance to phagocytosis on these bacteria (Poirier et al, 1989;Perez-Casal et al, 1992). Based on the results of Pancholi and Fischetti (1988) and Perez-Casal et al (1995), it could be inferred that the key domains associated with the antiphagocytic properties of the M proteins were located in the N-terminal and central portions of the M proteins.…”

Section: Introductionmentioning

confidence: 99%

M‐related protein (Mrp) contributes to group A streptococcal resistance to phagocytosis by human granulocytes

Podbielski¹,

Schnitzler²,

Beyhs³

et al. 1996

Molecular Microbiology

110

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The M protein has been postulated to be a major group A streptococcal (GAS) virulence factor because of its contribution to the bacterial resistance to opsonophagocytosis. Direct evidence of this was only provided for GAS strains which expressed a single M protein. The majority of GAS express additional, structurally similar M-related proteins, Mrp and Enn, which have been described as IgG- and IgA-binding proteins. To determine the involvement of Mrp and M protein in phagocytosis resistance, the mrp and emm genes from serotypes M2, M4, and M49 as well as from M-untypeable strain 64/14 were insertionally inactivated. The mrp and emm mutants were subjected to direct bactericidal assays. As judged by numbers of surviving colony-forming units, all mutant strains with the exception of the mrp4 mutant exhibited reduced multiplication factors as compared to the isogenic wild-type strains. Subsequent analysis of phagocytosis by flow cytometry, measuring association of BCECF/AM-labelled bacteria and granulocytes, paralleled the results from direct bactericidal assays regardless of whether isolated granulocytes or whole blood were utilized. Resistant wild-type GAS strains bound to less than 24% of granulocytes, whereas phagocytosis-sensitive controls attached to more than 90% of the white blood cells. 40 to 60% of the granulocytes associated with the mrp and emm mutants within 1 h of co-incubation. Kinetic data suggested that attachment to granulocytes proceeds faster for emm mutants than for corresponding mrp mutants. By adding a dihydro-rhodamine123 stain and measuring fluorescence induced by oxidative burst, the experimental data suggested that bacteria bound to granulocytes were also engulfed and integrated into phagolysosomes. Thus, these data indicated that, if present, both mrp and emm gene products contribute to phagocytosis resistance by decreasing bacterial binding to granulocytes.

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Processing of viable group A streptococci leads to major histocompatibility complex class II presentation of T cell epitopes from the major protective antigen

et al. 1994

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We have previously mapped major histocompatibility complex (MHC) class II-restricted T cell epitopes of the surface M protein of type 5 group A streptococci (M5) and show here that two out of four epitopes investigated were efficiently processed during incubation of viable streptococci with spleen cells for presentation to M5-specific murine T cell clones. Viable streptococci were processed more efficiently than heat-killed bacteria suggesting that secreted virulence factors of streptococci do not obstruct processing of streptococcal antigens in the dose range used. Epitopes from different regions of M5 could be ranked according to the efficiency with which they were processed, which may contribute to their relative immunodominance. It was further demonstrated that T cell clones specific for M5 308-319, an epitope from the M type conserved carboxy-terminal half of M5, cross-reacted between M5, M6 and M12, but not M49, streptococci. Helper T cell epitopes which are shared between streptococcal M types and are presented by MHC class II molecules on antigen-presenting cells after processing of viable streptococci could be particularly useful in the design of multivalent streptococcal vaccines.

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Fibrinogen binding and resistance to phagocytosis of Streptococcus sanguis expressing cloned M protein of Streptococcus pyogenes

Cited by 43 publications

References 19 publications

Characterization of a conserved helper-T-cell epitope from group A Streptococcal M proteins

Characterization of a conserved helper-T-cell epitope from group A Streptococcal M proteins

M‐related protein (Mrp) contributes to group A streptococcal resistance to phagocytosis by human granulocytes

Processing of viable group A streptococci leads to major histocompatibility complex class II presentation of T cell epitopes from the major protective antigen

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