This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ren, B.
Right arrow Articles by Briles, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ren, B.
Right arrow Articles by Briles, D. E.

 Previous Article  |  Next Article 

Infection and Immunity, January 2003, p. 75-85, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.75-85.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Both Family 1 and Family 2 PspA Proteins Can Inhibit Complement Deposition and Confer Virulence to a Capsular Serotype 3 Strain of Streptococcus pneumoniae

Bing Ren,1* Alexander J. Szalai,2 Orlanda Thomas,1 Susan K. Hollingshead,1 and David E. Briles1

Department of Microbiology,1 Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 352942

Received 2 July 2002/ Returned for modification 8 August 2002/ Accepted 23 September 2002

Pneumococcal surface protein A (PspA), a virulence factor of Streptococcus pneumoniae, is exceptionally diverse, being classified into two major families which are over 50% divergent by sequence analysis. A family 1 PspA from strain WU2 was previously shown to impede the clearance of pneumococci from mouse blood and to interfere with complement deposition on the bacterial surface. To determine whether a family 2 PspA can perform the same role as family 1 PspA, the family 1 PspA (from strain WU2) was replaced with a family 2 PspA (from strain TIGR4) by molecular genetic methods to make an isogenic pair of strains expressing different PspA proteins. Surface binding of lactoferrin and interference with C3 deposition by the two types of PspA proteins were determined by flow cytometry, and virulence was assessed in a mouse bacteremia model. Although the family 2 PspA appeared to bind less human lactoferrin than did the family 1 PspA, both PspA proteins could interfere with complement deposition on the pneumococcal surface and could provide full virulence in the mouse infection model. A mutant form of the family 2 PspA with a deletion within the choline-binding region was also produced. Pneumococci with this mutant PspA failed to bind human lactoferrin even though the PspA was present on the pneumococcal surface. The mutant PspA only partially interfered with complement deposition and moderately attenuated virulence. These results suggest that family 1 and family 2 PspA proteins play similar roles in virulence and that surface accessibility of PspA is important for their function.

* Corresponding author. Mailing address: 845 19th St. S., BBRB 658 Box 10, Birmingham, AL 35294. Phone: (205) 934-1880. Fax: (205) 934-0605. E-mail: bing_ren{at}microbio.uab.edu.

Editor: D. L. Burns

Infection and Immunity, January 2003, p. 75-85, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.75-85.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sabharwal, V., Ram, S., Figueira, M., Park, I. H., Pelton, S. I. (2009). Role of Complement in Host Defense against Pneumococcal Otitis Media. Infect. Immun. 77: 1121-1127 [Abstract] [Full Text]  
  • Melin, M., Jarva, H., Siira, L., Meri, S., Kayhty, H., Vakevainen, M. (2009). Streptococcus pneumoniae Capsular Serotype 19F Is More Resistant to C3 Deposition and Less Sensitive to Opsonophagocytosis than Serotype 6B. Infect. Immun. 77: 676-684 [Abstract] [Full Text]  
  • Lu, L., Ma, Z., Jokiranta, T. S., Whitney, A. R., DeLeo, F. R., Zhang, J.-R. (2008). Species-Specific Interaction of Streptococcus pneumoniae with Human Complement Factor H. J. Immunol. 181: 7138-7146 [Abstract] [Full Text]  
  • Chiavolini, D., Pozzi, G., Ricci, S. (2008). Animal Models of Streptococcus pneumoniae Disease. Clin. Microbiol. Rev. 21: 666-685 [Abstract] [Full Text]  
  • Melin, M. M., Hollingshead, S. K., Briles, D. E., Lahdenkari, M. I., Kilpi, T. M., Kayhty, H. M. (2008). Development of Antibodies to PspA Families 1 and 2 in Children after Exposure to Streptococcus pneumoniae. CVI 15: 1529-1535 [Abstract] [Full Text]  
  • Glover, D. T., Hollingshead, S. K., Briles, D. E. (2008). Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis. Infect. Immun. 76: 2767-2776 [Abstract] [Full Text]  
  • Li, J., Glover, D. T., Szalai, A. J., Hollingshead, S. K., Briles, D. E. (2007). PspA and PspC Minimize Immune Adherence and Transfer of Pneumococci from Erythrocytes to Macrophages through Their Effects on Complement Activation. Infect. Immun. 75: 5877-5885 [Abstract] [Full Text]  
  • Darrieux, M., Miyaji, E. N., Ferreira, D. M., Lopes, L. M., Lopes, A. P. Y., Ren, B., Briles, D. E., Hollingshead, S. K., Leite, L. C. C. (2007). Fusion Proteins Containing Family 1 and Family 2 PspA Fragments Elicit Protection against Streptococcus pneumoniae That Correlates with Antibody-Mediated Enhancement of Complement Deposition. Infect. Immun. 75: 5930-5938 [Abstract] [Full Text]  
  • Hammerschmidt, S., Agarwal, V., Kunert, A., Haelbich, S., Skerka, C., Zipfel, P. F. (2007). The Host Immune Regulator Factor H Interacts via Two Contact Sites with the PspC Protein of Streptococcus pneumoniae and Mediates Adhesion to Host Epithelial Cells. J. Immunol. 178: 5848-5858 [Abstract] [Full Text]  
  • Ogunniyi, A. D., LeMessurier, K. S., Graham, R. M. A., Watt, J. M., Briles, D. E., Stroeher, U. H., Paton, J. C. (2007). Contributions of Pneumolysin, Pneumococcal Surface Protein A (PspA), and PspC to Pathogenicity of Streptococcus pneumoniae D39 in a Mouse Model. Infect. Immun. 75: 1843-1851 [Abstract] [Full Text]  
  • LeMessurier, K. S., Ogunniyi, A. D., Paton, J. C. (2006). Differential expression of key pneumococcal virulence genes in vivo. Microbiology 152: 305-311 [Abstract] [Full Text]  
  • Hollingshead, S. K., Baril, L., Ferro, S., King, J., Coan, P., Briles, D. E., the Pneumococcal Proteins Epi Study Group, (2006). Pneumococcal surface protein A (PspA) family distribution among clinical isolates from adults over 50 years of age collected in seven countries. J Med Microbiol 55: 215-221 [Abstract] [Full Text]  
  • Ware, D., Jiang, Y., Lin, W., Swiatlo, E. (2006). Involvement of potD in Streptococcus pneumoniae Polyamine Transport and Pathogenesis. Infect. Immun. 74: 352-361 [Abstract] [Full Text]  
  • Ng, W.-L., Tsui, H.-C. T., Winkler, M. E. (2005). Regulation of the pspA Virulence Factor and Essential pcsB Murein Biosynthetic Genes by the Phosphorylated VicR (YycF) Response Regulator in Streptococcus pneumoniae. J. Bacteriol. 187: 7444-7459 [Abstract] [Full Text]  
  • Briles, D. E., Novak, L., Hotomi, M., van Ginkel, F. W., King, J. (2005). Nasal Colonization with Streptococcus pneumoniae Includes Subpopulations of Surface and Invasive Pneumococci. Infect. Immun. 73: 6945-6951 [Abstract] [Full Text]  
  • Yuste, J., Botto, M., Paton, J. C., Holden, D. W., Brown, J. S. (2005). Additive Inhibition of Complement Deposition by Pneumolysin and PspA Facilitates Streptococcus pneumoniae Septicemia. J. Immunol. 175: 1813-1819 [Abstract] [Full Text]  
  • Ren, B., McCrory, M. A., Pass, C., Bullard, D. C., Ballantyne, C. M., Xu, Y., Briles, D. E., Szalai, A. J. (2004). The Virulence Function of Streptococcus pneumoniae Surface Protein A Involves Inhibition of Complement Activation and Impairment of Complement Receptor-Mediated Protection. J. Immunol. 173: 7506-7512 [Abstract] [Full Text]  
  • Simmons, W. L., Denison, A. M., Dybvig, K. (2004). Resistance of Mycoplasma pulmonis to Complement Lysis Is Dependent on the Number of Vsa Tandem Repeats: Shield Hypothesis. Infect. Immun. 72: 6846-6851 [Abstract] [Full Text]  
  • Johnston, J. W., Myers, L. E., Ochs, M. M., Benjamin, W. H. Jr., Briles, D. E., Hollingshead, S. K. (2004). Lipoprotein PsaA in Virulence of Streptococcus pneumoniae: Surface Accessibility and Role in Protection from Superoxide. Infect. Immun. 72: 5858-5867 [Abstract] [Full Text]  
  • Shaper, M., Hollingshead, S. K., Benjamin, W. H. Jr., Briles, D. E. (2004). PspA Protects Streptococcus pneumoniae from Killing by Apolactoferrin, and Antibody to PspA Enhances Killing of Pneumococci by Apolactoferrin. Infect. Immun. 72: 5031-5040 [Abstract] [Full Text]  
  • Ren, B., Szalai, A. J., Hollingshead, S. K., Briles, D. E. (2004). Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface. Infect. Immun. 72: 114-122 [Abstract] [Full Text]  
  • Trzcinski, K., Thompson, C. M., Lipsitch, M. (2003). Construction of Otherwise Isogenic Serotype 6B, 7F, 14, and 19F Capsular Variants of Streptococcus pneumoniae Strain TIGR4. Appl. Environ. Microbiol. 69: 7364-7370 [Abstract] [Full Text]  
  • Pandiripally, V., Wei, L., Skerka, C., Zipfel, P. F., Cue, D. (2003). Recruitment of Complement Factor H-Like Protein 1 Promotes Intracellular Invasion by Group A Streptococci. Infect. Immun. 71: 7119-7128 [Abstract] [Full Text]  
  • Swiatlo, E., King, J., Nabors, G. S., Mathews, B., Briles, D. E. (2003). Pneumococcal Surface Protein A Is Expressed In Vivo, and Antibodies to PspA Are Effective for Therapy in a Murine Model of Pneumococcal Sepsis. Infect. Immun. 71: 7149-7153 [Abstract] [Full Text]  
  • Lu, L., Lamm, M. E., Li, H., Corthesy, B., Zhang, J.-R. (2003). The Human Polymeric Immunoglobulin Receptor Binds to Streptococcus pneumoniae via Domains 3 and 4. J. Biol. Chem. 278: 48178-48187 [Abstract] [Full Text]  
  • Roche, H., Ren, B., McDaniel, L. S., Hakansson, A., Briles, D. E. (2003). Relative Roles of Genetic Background and Variation in PspA in the Ability of Antibodies to PspA To Protect against Capsular Type 3 and 4 Strains of Streptococcus pneumoniae. Infect. Immun. 71: 4498-4505 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»