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Infection and Immunity, September 1999, p. 4517-4524, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Resistance to Both Complement Activation and Phagocytosis in Type 3 Pneumococci Is Mediated by the Binding of Complement Regulatory Protein Factor H

Chris Neeleman,1,2 Sibyl P. M. Geelen,1,3 Piet C. Aerts,1,3 Mohammed R. Daha,4 Tom E. Mollnes,5 John J. Roord,3 George Posthuma,6 Hans van Dijk,1 and André Fleer1,3,*

Department of Infectious Diseases, University Hospital for Children and Youth, "Het Wilhelmina Kinderziekenhuis,"3 and Eijkman-Winkler Laboratory of Medical Microbiology1 and Department of Cell Biology,6 University Medical Centre, Utrecht, University Hospital Nijmegen, Nijmegen,2 and University Hospital Leiden, Leiden,4 The Netherlands, and Nordland Central Hospital, Bødö, Norway5

Received 19 October 1998/Returned for modification 2 December 1998/Accepted 28 May 1999

To study the role of surface-associated proteins in the virulence of Streptococcus pneumoniae, we used two serotype 3 strains, ATCC 6303 and WU2, and two PspA-negative mutants of WU2, an encapsulated one, JY1123 (Caps+/PspA-), and an unencapsulated one, DW3.8 (Caps-/PspA-). ATCC 6303 and WU2 were highly virulent in mice, while the virulence of JY1123 was slightly decreased (50% lethal doses [LD50s], 24, 6, and 147 CFU/mouse, respectively); DW3.8 was avirulent (LD50, 2 × 108 CFU). In vitro, ATCC 6303, WU2, and JY1123 (Caps+/PspA-) strongly resisted complement activation and complement-dependent opsonophagocytosis, whereas DW3.8 (Caps-/PspA-) was easily phagocytized in fresh serum. Trypsin treatment of ATCC 6303, WU2, and JY1123 (Caps+/PspA-) resulted in enhanced complement activation and complement-dependent opsonophagocytosis. Trypsin had no deleterious effect on the polysaccharide capsule. In addition, trypsin pretreatment of ATCC 6303 strongly reduced virulence upon intraperitoneal challenge in mice. This indicated that surface proteins play a role in the resistance to complement activation and opsonophagocytosis and contribute to the virulence of type 3 pneumococci. In subsequent experiments, we could show that the modulation of complement activation was associated with surface components that bind complement regulator factor H; binding is trypsin sensitive and independent of prior complement activation. Immunoblotting of cell wall proteins of the virulent strain ATCC 6303 with anti-human factor H antibody revealed three factor H-binding proteins of 88, 150, and 196 kDa. Immunogold electron microscopy showed a close association of factor H-binding components with the outer surface of the cell wall. The role of these factor H-binding surface proteins in the virulence of pneumococci is interesting and warrants further investigation.

* Corresponding author. Mailing address: University Hospital for Children and Youth, "Het Wilhelmina Kinderziekenhuis," P.O. Box 85090, 3508 AB Utrecht, The Netherlands. Phone: (31) 30 2504001. Fax: (31) 30 2505349. E-mail: a.fleer{at}wkz.azu.nl.

Infection and Immunity, September 1999, p. 4517-4524, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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