Caries Y Endocarditis

yJ Pharmacol Sci 113, 120 – 125 (2010)

Journal of Pharmacological Sciences ©2010 The Japanese Pharmacological Society

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Roles of Oral Bacteria in Cardiovascular Diseases — From Molecular Mechanisms to Clinical Cases: Cell-Surface Structures of Novel Serotype k Streptococcus mutans Strains and Their Correlation to Virulence
Kazuhiko Nakano1, Ryota Nomura1, MichiyoMatsumoto1, and Takashi Ooshima1,*
1

Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan

Received November 16, 2009; Accepted December 21, 2009

Abstract. Streptococcus mutans is generally known as a pathogen of dental caries, and it is also considered to cause bacteremia and infective endocarditis (IE). S. mutans was previouslyclassified into 3 serotypes, c, e, and f, due to the different chemical compositions of the serotype-specific polysaccharides, which are composed of a rhamnose backbone and glucose side chains. We recently designated non-c/e/f serotype S. mutans strains as novel serotype k, which is characterized by a drastic reduction in the amount of the glucose side chain. A common biological feature of novel serotype-kstrains is a lower level of cariogenicity due to alterations of several major cell surface protein antigens. As for virulence in blood, these strains survive in blood for a longer duration due to lower antigenicity, while the detection rate of all strains carrying the gene encoding collagen-binding adhesin has been shown to be high. Furthermore, molecular biological analyses of infected heartvalve specimens obtained from IE patients revealed a high detection rate of serotype-k S. mutans. Together, these findings suggest that serotype-k S. mutans strains show low cariogenicity but high virulence in blood as compared to the other serotypes, due to alterations of several cell surface structures. Keywords: Streptococcus mutans, serotype, bacteremia, infective endocarditis, cell-surfaceantigen, oral bacteria 1. Introduction Streptococcus mutans is a member of the group of Gram-positive streptococci and generally known to be a major pathogen of dental caries, which is defined as the localized destruction of dental hard tissue by acid produced by the bacterium from sucrose via the glucosyltransferases (GTFs) (1). The organism has also been isolated from the blood of several patientswith bacteremia and infective endocarditis. S. mutans was previously classified into 3 serotypes (c, e, and f) based on the chemical composition of the cell-surface polysaccharide, which is composed of rhamnose and glucose polymers (2); and it has been reported that approximately 70% – 80% of S. mutans strains in the oral cavity belong
*Corresponding author. ooshima@dent.osaka-u.ac.jp Publishedonline in J-STAGE on May 24, 2010 (in advance) doi: 10.1254/jphs.09R24FM

to serotype c, followed by e (20%) and f (less than 5%) (3). The biosynthesis pathways of the serotype-specific rhamnose-glucose polymers have also been shown (Fig. 1), in which the rml (rmlA through rmlD) and gluA genes are involved with formation of the rhamnose backbone (dTDP-L-rhamnose) and glucose side-chain(UDP-Dglucose) from D-glucose-1-phosphate, respectively (4 – 6). Later, 6 genes (rgpA through rgpF) along with rgpG were shown to be related to the biosynthesis of rhamnose-glucose polymers, of which rgpE is considered to be involved in side chain formation by glucose units (7, 8). A wide variety of protein antigens of S. mutans have been characterized, among which GTFs, 190-kDa protein antigen (PA), andglucan-binding proteins (Gbps) are the most well known. S. mutans synthesizes adhesive glucans from sucrose by the action of GTFs, and those glucans mediate adherence of the bacterial cells to tooth surfaces (9). Three types of GTFs (GTFB, GTFC, and GTFD)

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Virulence of Serotype k S. mutans
D-glucose-1-phosphate

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rmlA, rmlB, rmlC, rmlD

gluA

lized collagen and laminin, it is...