INFECTION AND IMMUNITY, Jan. 2006, p. 740–743 Vol. 74, No. 1 0019-9567/06/$08.000 doi:10.1128/IAI.74.1.740–743.2006 Copyright © 2006, American Society for Microbiology. All Rights Reserved. Contribution of Sialic Acid-Binding Adhesin to Pathogenesis of Experimental Endocarditis Caused by Streptococcus gordonii DL1 Yukihiro Takahashi, 1 * Eizo Takashima, 1 Kisaki Shimazu, 2 Hisao Yagishita, 3 Takaaki Aoba, 3 and Kiyoshi Konishi 1 Department of Microbiology, 1 Department of Pediatric Dentistry, 2 and Department of Pathology, 3 Nippon Dental University School of Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan Received 18 May 2005/Returned for modification 29 August 2005/Accepted 21 October 2005 An insertional mutation in hsa, the gene encoding the sialic acid-binding adhesin of Streptococcus gordonii DL1, resulted in a significant reduction of the infection rate of the organism and an inflammatory reaction in the rat aortic valve with experimental endocarditis, suggesting that the adhesin contributes to the infectivity of the organism for heart valves. Streptococcus gordonii and other closely related species col- onize primarily the human tooth surface as members of the biofilm community commonly referred to as dental plaque (6, 7, 10). In addition, these streptococci are well known for their ability to colonize damaged heart valves and are the most frequently identified bacteria as primary etiological agents of infective endocarditis (1, 2, 5). We have previously reported that the sialic acid-binding adhesin (Hsa) of S. gordonii DL1 may contribute not only to oral colonization but also to the pathogenesis of infective endocarditis (21, 22, 23, 24). The neuraminidase-sensitive adhesive properties of viridans group streptococci have been primarily found as adhesions to saliva-coated hydroxyapatite, an experimental model of the tooth surface, and also to platelets and host cells including erythrocytes and polymorphonuclear leukocytes (6, 7, 10, 17, 18, 24). A specific cell surface antigen of S. gordonii DL1 has been associated with its adhesive properties (21). The gene for this antigen, hsa, has been cloned, and the protein, Hsa, en- coded by hsa has been identified as the sialic acid-binding adhesin (22). Hsa is a large serine-rich repeat protein com- posed of 2,178 amino acid residues (22). The carboxyl-terminal serine-rich repetitive region, which accounts for over 75% of the length of Hsa, is glycosylated containing GlcNAc (21, 24). The glycosylation may confer an extended rod-shaped confor- mation on the serine-rich region, enabling this region to func- tion as a molecular stalk for cell surface presentation of the putative amino-terminal receptor-binding domain (24). Hsa binds 2-3-linked sialic acid termini of O-glycosylated mucin- type glycoproteins, including salivary mucin MG2, platelet gly- coprotein Ib, and leukosialin, the major surface glycoprotein of human polymorphonuclear leukocytes (3, 18, 19, 22, 23, 24, 25). Moreover, fibronectin and platelet glycoprotein IIb, an- other platelet sialoglycoprotein, have been identified as recep- tors for Hsa (25; N. S. Jakubovics, L. C. Dutton, A. H. Nobbs, and H. F. Jenkinson, Abstr. 82nd Gen. Session Exhibition Int. Assoc. Dent. Res., abstr. 4000, 2004). The present study evaluated the contribution of Hsa to the pathogenesis of infective endocarditis in rats with catheter- induced vegetations. For this purpose, the infectivities of the wild-type and hsa mutant S. gordonii strains were compared. * Corresponding author. Mailing address: Department of Microbi- ology, Nippon Dental University School of Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. Phone: 81-3-3261-8763. Fax: 81-3-3264-8399. E-mail: biseibut@tky.ndu.ac.jp. FIG. 1. Bacterial density in vegetations infected with S. gordonii DL1 (filled dots) or EM230 (open dots). Each dot in a column represents the bacterial density in a vegetation (log 10 CFU/mg of vegetation) in a single rat. Dots below the zero level represent culture-negative vegetations. Differences in median vegetation bacterial densities and differences in rates of valve infections were evaluated by the Mann-Whitney U test and Fisher’s exact probability test, respectively. N.S., not significant. 740