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Infection and Immunity, October 2002, p. 5604-5611, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5604-5611.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Human Complement Regulator Factor H Binds Pneumococcal Surface Protein PspC via Short Consensus Repeats 13 to 15

Thomas G. Duthy,1 Rebecca J. Ormsby,1 Eleni Giannakis,1 A. David Ogunniyi,2 Uwe H. Stroeher,2 James C. Paton,2 and David L. Gordon1*

Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, South Australia 5042,1 Department of Molecular BioSciences, Adelaide University, Adelaide, South Australia 5005, Australia2

Received 4 April 2002/ Returned for modification 22 May 2002/ Accepted 10 June 2002

The innate ability of Streptococcus pneumoniae to resist complement activation and complement-mediated phagocytosis may be a direct consequence of the ability of the bacteria to bind components of the complement regulatory system. One such component, factor H (fH), is a crucial fluid-phase negative regulator of the alternative pathway of complement and is utilized by a number of pathogenic organisms to resist complement attack. The pneumococcal surface protein C (PspC [also known as CbpA] and SpsA) has been shown to bind fH, although the exact binding site within one or more of the 20 short consensus repeats (SCRs) of the molecule is not known. The purpose of the current study was to map specific SCRs on fH responsible for this binding. Initial experiments utilizing type 2 pneumococcal strain D39 and its isogenic PspC-negative derivative (D39/pspC mutant) showed that fH binding was PspC dependent. A purified recombinant protein derivative of PspC that lacked the proline-rich region (PspC{Delta}Pro) had a reduced binding efficiency for fH, thereby directly showing the importance of this region for the fH interaction. We have specifically shown by inhibition experiments that SCRs responsible for heparin and C3b binding of fH are not involved in binding PspC and the interaction between fH and PspC is largely hydrophobic, since no inhibition was observed in the presence of high concentrations of NaCl. Construction of SCR proteins encompassing the whole fH molecule showed that SCRs 8 to 15 (SCR 8-15) mediated binding to PspC. Further localization experiments revealed that SCR 13 and SCR 15 were required for full binding, although partial binding was retained when either SCR was removed.

* Corresponding author. Mailing address: Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, SA 5042, Australia. Phone: 61-8-8204-5252. Fax: 61-8-8204-4733. E-mail: d.gordon{at}flinders.edu.au.

Editor: E. I. Tuomanen

Infection and Immunity, October 2002, p. 5604-5611, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5604-5611.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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