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* Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208;
Department of Bacteriology and Immunology, Haartman Institute and HUSLAB, University of Helsinki, Helsinki, Finland; and
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840
Streptococcus pneumoniae naturally colonizes the nasopharynx as a commensal organism and sometimes causes infections in remote tissue sites. This bacterium is highly capable of resisting host innate immunity during nasopharyngeal colonization and disseminating infections. The ability to recruit complement factor H (FH) by S. pneumoniae has been implicated as a bacterial immune evasion mechanism against complement-mediated bacterial clearance because FH is a complement alternative pathway inhibitor. S. pneumoniae recruits FH through a previously defined FH binding domain of choline-binding protein A (CbpA), a major surface protein of S. pneumoniae. In this study, we show that CbpA binds to human FH, but not to the FH proteins of mouse and other animal species tested to date. Accordingly, deleting the FH binding domain of CbpA in strain D39 did not result in obvious change in the levels of pneumococcal bacteremia or virulence in a bacteremia mouse model. Furthermore, this species-specific pneumococcal interaction with FH was shown to occur in multiple pneumococcal isolates from the blood and cerebrospinal fluid. Finally, our phagocytosis experiments with human and mouse phagocytes and complement systems provide additional evidence to support our hypothesis that CbpA acts as a bacterial determinant for pneumococcal resistance to complement-mediated host defense in humans.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and by a research grant from the National Institutes of Health/National Institutes of Deafness and Other Communication Disorders (DC006917).
2 Address correspondence and reprint requests to Dr. Jing-Ren Zhang, Center for Immunology and Microbial Disease, Albany Medical College, M/C 151, Room MS453, 47 New Scotland Avenue, Albany, NY 12208. E-mail address: zhangj{at}mail.amc.edu
3 Abbreviations used in this paper: FH, factor H; CbpA, choline-binding protein A; pIgR, polymeric IgR; PMN, polymorphonuclear leukocyte; PVDF, polyvinylidene difluoride; RPMI/H, RPMI 1640 medium buffered with 10 mM HEPES; SC, secretory component; SIgA, secretory IgA.
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