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J. Biol. Chem., Vol. 281, Issue 9, 5515-5521, March 3, 2006

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Serum Opacity Factor, a Streptococcal Virulence Factor That Binds to Apolipoproteins A-I and A-II and Disrupts High Density Lipoprotein Structure^*

Harry S. Courtney¹, Yong-Mei Zhang, Matthew W. Frank, and Charles O. Rock

From the Veterans Affairs Medical Center and Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38104 and the Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Serum opacity factor (SOF) is a virulence determinant of group A streptococci that opacifies mammalian sera. We analyzed the specificity and mechanism of the opacity reaction using a recombinant form of the amino-terminal opacification domain of SOF, rSOF. Our data indicate that rSOF is neither a protease nor a lipase, but rather it is the binding of rSOF to high density lipoprotein (HDL) that triggers the opacity reaction. rSOF did not opacify plasma from apoA-I^–/– mice or purified low or very low density lipoproteins but readily opacified HDL. rSOF binding to HDL was characterized by two high affinity binding sites; it bound to apoA-I (K_d = 6 nM) and apoA-II (K_d = 30 nM), and both apoA-I and apoA-II blocked the binding of rSOF to HDL. Electron microscopic examination and biochemical analyses of HDL treated with rSOF revealed the formation of lipid droplets devoid of apolipoproteins. Thus, SOF interacts with HDL in human blood by binding to apoA-I and apoA-II and causing the release of HDL lipid cargo, which coalesces to form lipid droplets, resulting in opacification. The disruption of HDL may attenuate its anti-inflammatory functions and contribute to the pathogenesis of group A streptococcal infections.

Received for publication, November 22, 2005 , and in revised form, December 22, 2005.

^* This work was supported by research funds from the Department of Veterans Affairs (to H. S. C.), National Institutes of Health Grant GM 34496 (to C. O. R.), Cancer Center (CORE) Support Grant CA 21765, and the American Lebanese Syrian Associated Charities. 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 To whom correspondence should be addressed: Veterans Affairs Medical Center, Research Service (151), 1030 Jefferson Ave., Memphis, TN 38104. Tel.: 901-523-8990, ext. 7548; Fax: 901-577-7273; E-mail: hcourtney{at}utmem.edu.

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