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J. Biol. Chem., Vol. 280, Issue 39, 33228-33239, September 30, 2005

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Streptococcus pyogenes Collagen Type I-binding Cpa Surface Protein

EXPRESSION PROFILE, BINDING CHARACTERISTICS, BIOLOGICAL FUNCTIONS, AND POTENTIAL CLINICAL IMPACT^*

From the Department of Medical Microbiology and Hospital Hygiene, Hospital of Rostock University, Schillingallee 70, D-18057 Rostock, Germany

The Streptococcus pyogenes collagen type I-binding protein Cpa (collagen-binding protein of group A streptococci) expressed by 28 serotypes of group A streptococci has been extensively characterized at the gene and protein levels. Evidence for three distinct families of cpa genes was found, all of which shared a common sequence encoding a 60-amino acid domain that accounted for selective binding to type I collagen. Surface plasmon resonance-based affinity measurements and functional studies indicated that the expression of Cpa was consistent with an attachment role for bacteria to tissue containing collagen type I. A cpa mutant displayed a significantly decreased internalization rate when incubated with HEp-2 cells but had no effect on the host cell viability. By utilizing serum from patients with a positive titer for streptolysin/DNase antibody, an increased anti-Cpa antibody titer was noted for patients with a clinical history of arthritis or osteomyelitis. Taken together, these results suggest Cpa may be a relevant matrix adhesin contributing to the pathogenesis of S. pyogenes infection of bones and joints.

Received for publication, March 16, 2005 , and in revised form, July 12, 2005.

^* 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.

The on-line version of this article (available at http://www.jbc.org) contains Figs. s1–s3.

¹ Supported by Deutsche Forschungsgemeinschaft Grants Po391/9-1, Po391/9-2, Po391/11-1, Po391/11-2, and Po391/12-1.

² To whom correspondence should be addressed. Tel.: 49-381-494-5900; Fax: 49-381-494-5902; E-mail: andreas.podbielski{at}med.uni-rostock.de.

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