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Infection and Immunity, April 1999, p. 1683-1687, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification of Pneumococcal Surface Protein A as a Lactoferrin-Binding Protein of Streptococcus pneumoniae

Sven Hammerschmidt, Gesina Bethe, Petra H. Remane, and Gursharan S. Chhatwal*

Department of Microbial Pathogenesis, GBF-National Research Centre for Biotechnology, 38106 Braunschweig, Germany

Received 28 September 1998/Returned for modification 17 December 1998/Accepted 12 January 1999

Lactoferrin (Lf), an iron-sequestering glycoprotein, predominates in mucosal secretions, where the level of free extracellular iron (10-18 M) is not sufficient for bacterial growth. This represents a mechanism of resistance to bacterial infections by prevention of colonization of the host by pathogens. In this study we were able to show that Streptococcus pneumoniae specifically recognizes and binds the iron carrier protein human Lf (hLf). Pretreatment of pneumococci with proteases reduced hLf binding significantly, indicating that the hLf receptor is proteinaceous. Binding assays performed with 63 clinical isolates belonging to different serotypes showed that 88% of the tested isolates interacted with hLf. Scatchard analysis showed the existence of two hLf-binding proteins with dissociation constants of 5.7 × 10-8 and 2.74 × 10-7 M. The receptors were purified by affinity chromatography, and internal sequence analysis revealed that one of the S. pneumoniae proteins was homologous to pneumococcal surface protein A (PspA). The function of PspA as an hLf-binding protein was confirmed by the ability of purified PspA to bind hLf and to competitively inhibit hLf binding to pneumococci. S. pneumoniae may use the hLf-PspA interaction to overcome the iron limitation at mucosal surfaces, and this might represent a potential virulence mechanism.

* Corresponding author. Mailing address: Dept. of Microbial Pathogenesis, GBF-National Research Centre for Biotechnology, Spielmannstrasse 7, 38106 Braunschweig, Germany. Phone: (531)-391-5860. Fax: (531)-391-5858. E-mail: GSC{at}GBF.de.

Infection and Immunity, April 1999, p. 1683-1687, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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