Journal of Experimental Medicine, Vol 177, 1593-1603, Copyright © 1993 by Rockefeller University Press

ARTICLES

Protein rib: a novel group B streptococcal cell surface protein that confers protective immunity and is expressed by most strains causing invasive infections

M Stalhammar-Carlemalm, L Stenberg and G Lindahl
Department of Medical Microbiology, University of Lund, Sweden.

The group B Streptococcus, an important cause of invasive infections in the neonate, is classified into four major serotypes (Ia, Ib, II, and III) based on the structure of the polysaccharide capsule. Since the capsule is a known virulence factor, it has been extensively studied, in particular in type III strains, which cause the majority of invasive infections. Two cell surface proteins, alpha and beta, have also been studied in detail since they confer protective immunity, but these proteins are usually not expressed by type III strains. We describe here a cell surface protein, designated protein Rib (resistance to proteases, immunity, group B), that confers protective immunity and is expressed by most strains of type III. Protein Rib was first identified as a distinct 95-kD protein in extracts of a type III strain, and was purified to homogeneity from that strain. Rabbit antiserum to protein Rib was used to demonstrate that it is expressed on the cell surface of 31 out of 33 type III strains, but only on 1 out of 25 strains representing the other three serotypes. Mouse protection tests showed that antiserum to protein Rib protects against lethal infection with three different strains expressing this antigen, including a strain representing a recently identified high virulence type III clone. Protein Rib is immunologically unrelated to the alpha and beta proteins, but shares several features with the alpha protein. Most importantly, the NH2-terminal amino acid sequences of the Rib and alpha proteins are identical at 6 out of 12 positions. In addition, both protein Rib and the alpha protein are relatively resistant to trypsin (and Rib is also resistant to pepsin) and both proteins vary greatly in size between different clinical isolates. Finally, both protein Rib and the alpha protein exhibit a regular ladderlike pattern in immunoblotting experiments, which may reflect a repetitive structure. Taken together, these data suggest that the Rib and alpha proteins are members of a family of proteins with related structure and function. Since protein Rib confers protective immunity, it may be valuable for the development of a protein vaccine against the group B Streptococcus, an encapsulated bacterium.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Yang, H.-H., Mascuch, S. J., Madoff, L. C., Paoletti, L. C. (2008). Recombinant Group B Streptococcus Alpha-Like Protein 3 Is an Effective Immunogen and Carrier Protein. CVI 15: 1035-1041 [Abstract] [Full Text]  
• Yang, H.-H., Madoff, L. C., Guttormsen, H.-K., Liu, Y.-D., Paoletti, L. C. (2007). Recombinant Group B Streptococcus Beta C Protein and a Variant with the Deletion of Its Immunoglobulin A-Binding Site Are Protective Mouse Maternal Vaccines and Effective Carriers in Conjugate Vaccines. Infect. Immun. 75: 3455-3461 [Abstract] [Full Text]  
• Ip, M., Cheuk, E. S. C., Tsui, M. H. Y., Kong, F., Leung, T. N., Gilbert, G. L. (2006). Identification of a Streptococcus agalactiae Serotype III Subtype 4 Clone in Association with Adult Invasive Disease in Hong Kong. J. Clin. Microbiol. 44: 4252-4254 [Abstract] [Full Text]  
• Larsson, C, Lindroth, M, Nordin, P, Stalhammar-Carlemalm, M, Lindahl, G, Krantz, I (2006). Association between low concentrations of antibodies to protein {alpha} and Rib and invasive neonatal group B streptococcal infection.. Arch. Dis. Child. Fetal Neonatal Ed. 91: F403-F408 [Abstract] [Full Text]  
• Zhang, S., Green, N. M., Sitkiewicz, I., LeFebvre, R. B., Musser, J. M. (2006). Identification and Characterization of an Antigen I/II Family Protein Produced by Group A Streptococcus. Infect. Immun. 74: 4200-4213 [Abstract] [Full Text]  
• Seifert, K. N., Adderson, E. E., Whiting, A. A., Bohnsack, J. F., Crowley, P. J., Brady, L. J. (2006). A unique serine-rich repeat protein (Srr-2) and novel surface antigen ({varepsilon}) associated with a virulent lineage of serotype III Streptococcus agalactiae.. Microbiology 152: 1029-1040 [Abstract] [Full Text]  
• Waldemarsson, J., Areschoug, T., Lindahl, G., Johnsson, E. (2006). The Streptococcal Blr and Slr Proteins Define a Family of Surface Proteins with Leucine-Rich Repeats: Camouflaging by Other Surface Structures. J. Bacteriol. 188: 378-388 [Abstract] [Full Text]  
• Zhao, Z., Kong, F., Gilbert, G. L. (2006). Reverse Line Blot Assay for Direct Identification of Seven Streptococcus agalactiae Major Surface Protein Antigen Genes. CVI 13: 145-149 [Abstract] [Full Text]  
• Maeland, J. A., Bevanger, L., Lyng, R. V. (2005). Immunological Markers of the R4 Protein of Streptococcus agalactiae. CVI 12: 1305-1310 [Abstract] [Full Text]  
• Price, J. D., Schaumburg, J., Sandin, C., Atkinson, J. P., Lindahl, G., Kemper, C. (2005). Induction of a Regulatory Phenotype in Human CD4+ T Cells by Streptococcal M Protein. J. Immunol. 175: 677-684 [Abstract] [Full Text]  
• Maione, D., Margarit, I., Rinaudo, C. D., Masignani, V., Mora, M., Scarselli, M., Tettelin, H., Brettoni, C., Iacobini, E. T., Rosini, R., D'Agostino, N., Miorin, L., Buccato, S., Mariani, M., Galli, G., Nogarotto, R., Dei, V. N., Vegni, F., Fraser, C., Mancuso, G., Teti, G., Madoff, L. C., Paoletti, L. C., Rappuoli, R., Kasper, D. L., Telford, J. L., Grandi, G. (2005). Identification of a Universal Group B Streptococcus Vaccine by Multiple Genome Screen. Science 309: 148-150 [Abstract] [Full Text]  
• Lalioui, L., Pellegrini, E., Dramsi, S., Baptista, M., Bourgeois, N., Doucet-Populaire, F., Rusniok, C., Zouine, M., Glaser, P., Kunst, F., Poyart, C., Trieu-Cuot, P. (2005). The SrtA Sortase of Streptococcus agalactiae Is Required for Cell Wall Anchoring of Proteins Containing the LPXTG Motif, for Adhesion to Epithelial Cells, and for Colonization of the Mouse Intestine. Infect. Immun. 73: 3342-3350 [Abstract] [Full Text]  
• Seepersaud, R., Hanniffy, S. B., Mayne, P., Sizer, P., Le Page, R., Wells, J. M. (2005). Characterization of a Novel Leucine-Rich Repeat Protein Antigen from Group B Streptococci That Elicits Protective Immunity. Infect. Immun. 73: 1671-1683 [Abstract] [Full Text]  
• Lindahl, G., Stalhammar-Carlemalm, M., Areschoug, T. (2005). Surface Proteins of Streptococcus agalactiae and Related Proteins in Other Bacterial Pathogens. Clin. Microbiol. Rev. 18: 102-127 [Abstract] [Full Text]  
• Aoyagi, Y., Adderson, E. E., Min, J. G., Matsushita, M., Fujita, T., Takahashi, S., Okuwaki, Y., Bohnsack, J. F. (2005). Role of L-Ficolin/Mannose-Binding Lectin-Associated Serine Protease Complexes in the Opsonophagocytosis of Type III Group B Streptococci. J. Immunol. 174: 418-425 [Abstract] [Full Text]  
• Maeland, J. A., Bevanger, L., Lyng, R. V. (2004). Antigenic Determinants of Alpha-Like Proteins of Streptococcus agalactiae. CVI 11: 1035-1039 [Abstract] [Full Text]  
• Jarva, H., Hellwage, J., Jokiranta, T. S., Lehtinen, M. J., Zipfel, P. F., Meri, S. (2004). The Group B Streptococcal {beta} and Pneumococcal Hic Proteins Are Structurally Related Immune Evasion Molecules That Bind the Complement Inhibitor Factor H in an Analogous Fashion. J. Immunol. 172: 3111-3118 [Abstract] [Full Text]  
• Leavis, H., Top, J., Shankar, N., Borgen, K., Bonten, M., van Embden, J., Willems, R. J. L. (2004). A Novel Putative Enterococcal Pathogenicity Island Linked to the esp Virulence Gene of Enterococcus faecium and Associated with Epidemicity. J. Bacteriol. 186: 672-682 [Abstract] [Full Text]  
• Larsson, C., Holmgren, J., Lindahl, G., Bergquist, C. (2004). Intranasal Immunization of Mice with Group B Streptococcal Protein Rib and Cholera Toxin B Subunit Confers Protection against Lethal Infection. Infect. Immun. 72: 1184-1187 [Abstract] [Full Text]  
• Carlsson, F., Berggard, K., Stalhammar-Carlemalm, M., Lindahl, G. (2003). Evasion of Phagocytosis through Cooperation between Two Ligand-binding Regions in Streptococcus pyogenes M Protein. J. Exp. Med. 198: 1057-1068 [Abstract] [Full Text]  
• Moyo, S. R., Maeland, J. A. (2003). Antibodies raised in animals against the Streptococcus agalactiae proteins c{alpha} and R4 and normal human serum antibodies target distinct epitopes. J Med Microbiol 52: 379-383 [Abstract] [Full Text]  
• Areschoug, T., Linse, S., Stalhammar-Carlemalm, M., Heden, L.-O., Lindahl, G. (2002). A Proline-Rich Region with a Highly Periodic Sequence in Streptococcal {beta} Protein Adopts the Polyproline II Structure and Is Exposed on the Bacterial Surface. J. Bacteriol. 184: 6376-6383 [Abstract] [Full Text]  
• Martin, D., Rioux, S., Gagnon, E., Boyer, M., Hamel, J., Charland, N., Brodeur, B. R. (2002). Protection from Group B Streptococcal Infection in Neonatal Mice by Maternal Immunization with Recombinant Sip Protein. Infect. Immun. 70: 4897-4901 [Abstract] [Full Text]  
• Nagano, N., Nagano, Y., Taguchi, F. (2002). High Expression of a C Protein {beta} Antigen Gene among Invasive Strains from Certain Clonally Related Groups of Type Ia and Ib Group B Streptococci. Infect. Immun. 70: 4643-4649 [Abstract] [Full Text]  
• MOYO, S. R., MAELAND, J. A., BERGH, K. (2002). Typing of human isolates of Streptococcus agalactiae (group B streptococcus, GBS) strains from Zimbabwe. J Med Microbiol 51: 595-662 [Abstract] [Full Text]  
• Areschoug, T., Stalhammar-Carlemalm, M., Karlsson, I., Lindahl, G. (2002). Streptococcal beta Protein Has Separate Binding Sites for Human Factor H and IgA-Fc. J. Biol. Chem. 277: 12642-12648 [Abstract] [Full Text]  
• Erdogan, S., Fagan, P. K., Talay, S. R., Rohde, M., Ferrieri, P., Flores, A. E., Guzman, C. A., Walker, M. J., Chhatwal, G. S. (2002). Molecular Analysis of Group B Protective Surface Protein, a New Cell Surface Protective Antigen of Group B Streptococci. Infect. Immun. 70: 803-811 [Abstract] [Full Text]  
• Kong, F., Gowan, S., Martin, D., James, G., Gilbert, G. L. (2002). Molecular Profiles of Group B Streptococcal Surface Protein Antigen Genes: Relationship to Molecular Serotypes. J. Clin. Microbiol. 40: 620-626 [Abstract] [Full Text]  
• Bohnsack, J. F., Whiting, A. A., Bradford, R. D., Van Frank, B. K., Takahashi, S., Adderson, E. E. (2002). Long-Range Mapping of the Streptococcus agalactiae Phylogenetic Lineage Restriction Digest Pattern Type III-3 Reveals Clustering of Virulence Genes. Infect. Immun. 70: 134-139 [Abstract] [Full Text]  
• Moyo, S. R., Maeland, J. A., Mudzori, J. (2001). Antibodies against Streptococcus agalactiae Proteins calpha and R4 in Sera from Pregnant Women from Norway and Zimbabwe. CVI 8: 1110-1114 [Abstract] [Full Text]  
• Puopolo, K. M., Hollingshead, S. K., Carey, V. J., Madoff, L. C. (2001). Tandem Repeat Deletion in the Alpha C Protein of Group B Streptococcus Is recA Independent. Infect. Immun. 69: 5037-5045 [Abstract] [Full Text]  
• Rioux, S., Martin, D., Ackermann, H.-W., Dumont, J., Hamel, J., Brodeur, B. R. (2001). Localization of Surface Immunogenic Protein on Group B Streptococcus. Infect. Immun. 69: 5162-5165 [Abstract] [Full Text]  
• Brodeur, B. R., Boyer, M., Charlebois, I., Hamel, J., Couture, F., Rioux, C. R., Martin, D. (2000). Identification of Group B Streptococcal Sip Protein, Which Elicits Cross-Protective Immunity. Infect. Immun. 68: 5610-5618 [Abstract] [Full Text]  
• Lachenauer, C. S., Creti, R., Michel, J. L., Madoff, L. C. (2000). Mosaicism in the alpha-like protein genes of group B streptococci. Proc. Natl. Acad. Sci. USA 97: 9630-9635 [Abstract] [Full Text]  
• Hedegaard, J., Hauge, M., Fage-Larsen, J., Mortensen, K. K., Kilian, M., Sperling-Petersen, H. U., Poulsen, K. (2000). Investigation of the translation-initiation factor IF2 gene, infB, as a tool to study the population structure of Streptococcus agalactiae. Microbiology 146: 1661-1670 [Abstract] [Full Text]  
• Areschoug, T., Stalhammar-Carlemalm, M., Larsson, C., Lindahl, G. (1999). Group B Streptococcal Surface Proteins as Targets for Protective Antibodies: Identification of Two Novel Proteins in Strains of Serotype V. Infect. Immun. 67: 6350-6357 [Abstract] [Full Text]  
• Lee, M. H., Nittayajarn, A., Ross, R. P., Rothschild, C. B., Parsonage, D., Claiborne, A., Rubens, C. E. (1999). Characterization of Enterococcus faecalis Alkaline Phosphatase and Use in Identifying Streptococcus agalactiae Secreted Proteins. J. Bacteriol. 181: 5790-5799 [Abstract] [Full Text]  
• Ross, R. A., Madoff, L. C., Paoletti, L. C. (1999). Regulation of Cell Component Production by Growth Rate in the Group B Streptococcus. J. Bacteriol. 181: 5389-5394 [Abstract] [Full Text]  
• Gravekamp, C., Kasper, D. L., Paoletti, L. C., Madoff, L. C. (1999). Alpha C Protein as a Carrier for Type III Capsular Polysaccharide and as a Protective Protein in Group B Streptococcal Vaccines. Infect. Immun. 67: 2491-2496 [Abstract] [Full Text]  
• Navarre, W. W., Schneewind, O. (1999). Surface Proteins of Gram-Positive Bacteria and Mechanisms of Their Targeting to the Cell Wall Envelope. Microbiol. Mol. Biol. Rev. 63: 174-229 [Abstract] [Full Text]  
• Shankar, V., Baghdayan, A. S., Huycke, M. M., Lindahl, G., Gilmore, M. S. (1999). Infection-Derived Enterococcus faecalis Strains Are Enriched in esp, a Gene Encoding a Novel Surface Protein. Infect. Immun. 67: 193-200 [Abstract] [Full Text]  
• Gravekamp, C., Rosner, B., Madoff, L. C. (1998). Deletion of Repeats in the Alpha C Protein Enhances the Pathogenicity of Group B Streptococci in Immune Mice. Infect. Immun. 66: 4347-4354 [Abstract] [Full Text]  
• Schuchat, A. (1998). Epidemiology of Group B Streptococcal Disease in the United States: Shifting Paradigms. Clin. Microbiol. Rev. 11: 497-513 [Abstract] [Full Text]  
• Kotarsky, H., Hellwage, J., Johnsson, E., Skerka, C., Svensson, H. G., Lindahl, G., Sjobring, U., Zipfel, P. F. (1998). Identification of a Domain in Human Factor H and Factor H-Like Protein-1 Required for the Interaction with Streptococcal M Proteins. J. Immunol. 160: 3349-3354 [Abstract] [Full Text]  
• Li, J., Kasper, D. L., Ausubel, F. M., Rosner, B., Michel, J. L. (1997). Inactivation of the alpha  C protein antigen gene, bca, by a novel shuttle/suicide vector results in attenuation of virulence and immunity in group B Streptococcus. Proc. Natl. Acad. Sci. USA 94: 13251-13256 [Abstract] [Full Text]  
• Wastfelt, M., Stalhammar-Carlemalm, M., Delisse, A.-M., Cabezon, T., Lindahl, G. (1996). Identification of a Family of Streptococcal Surface Proteins with Extremely Repetitive Structure. J. Biol. Chem. 271: 18892-18897 [Abstract] [Full Text]  
• Pleass, R. J., Areschoug, T., Lindahl, G., Woof, J. M. (2001). Streptococcal IgA-binding Proteins Bind in the Calpha 2-Calpha 3 Interdomain Region and Inhibit Binding of IgA to Human CD89. J. Biol. Chem. 276: 8197-8204 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS