Molecular and clinical analyses of the gene encoding the collagen-binding adhesin of Streptococcus mutans

Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
Journal of Medical Microbiology (Impact Factor: 2.25). 04/2009; 58(Pt 4):469-75. DOI: 10.1099/jmm.0.007559-0
Source: PubMed


Streptococcus mutans is a known pathogen of dental caries and its major cell surface antigens have been widely investigated. Recently, an approximately 120 kDa Cnm protein with binding properties to type I collagen was identified, and its encoding gene (cnm) cloned and sequenced. In the present study, we sequenced cnm from 47 different clinical S. mutans strains and found that the nucleotide alignment of the collagen-binding domain was well conserved. We devised a PCR method for identifying the cnm gene, examined the prevalence of cnm-positive S. mutans strains in various mother-child groups, and assessed the significance of such strains for transmission and dental caries. The detection rate of cnm-positive strains was significantly lower in strains isolated from Japanese children in the 2000s (8.0 %) as compared to those isolated in the 1980s (15.8 %) (P<0.05). Furthermore, the presence of S. mutans possessing cnm in salivary specimens collected from 55 S. mutans-positive mother-child pairs was 40 and 32.7 % in the mothers and children, respectively. The frequency of cnm-positive children whose mothers were also positive was 72 %, which was significantly higher than that of cnm-positive children with negative mothers (P<0.0001, odds ratio 17.5). In addition, clinical parameters indicating dental caries were significantly increased in children with cnm-positive S. mutans in saliva (n=13), as compared to those with cnm-negative S. mutans (n=15) and S. mutans-negative children (n=20) (P<0.01). These results indicate that cnm-positive S. mutans strains are closely correlated with dental caries, while vertical transmission in cnm-positive mother-child pairs was also demonstrated.

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    • "Binding to fibronectin is also mediated by FBP-130 and FnB, illustrating the redundant ability of multiple adhesins in interactions with ECM components (Chia et al., 2000). A number of studies have revealed that 10–20% of S. mutans clinical isolates express a collagen (and laminin) binding protein named Cnm (Sato et al., 2004; Nomura et al., 2009; Nakano et al., 2010). The Cnm protein is composed of a conserved collagen-binding domain (A domain), a threonine-rich repeat region (B domain) that is followed by a C-terminal LPXTG motif for anchoring to the cell wall (Sato et al., 2004). "
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    ABSTRACT: Cnm, a collagen- and laminin-binding protein present in a subset of S. mutans strains, mediates binding to extracellular matrices (ECM), intracellular invasion and virulence in the Galleria mellonella model. Antibodies raised against Cnm were used to confirm expression and the cell surface localization of Cnm in the highly invasive OMZ175 strain. Sequence analysis identified two additional genes (cnaB and cbpA) encoding putative surface proteins immediately upstream of cnm. Inactivation of cnaB and cbpA in OMZ175, individually or in combination did not decrease the ability of this highly invasive and virulent strain to bind to different ECM proteins, invade human coronary artery endothelial cells (HCAEC), or to kill G. mellonella. Similarly, expression of cnaB and cbpA in the cnm- strain UA159 revealed that these genes did not enhance Cnm-related phenotypes. However, integration of cnm in the chromosome of UA159 significantly increased its ability to bind to collagen and laminin, invade HCAEC, and kill G. mellonella. Moreover, the presence of antibodies against Cnm nearly abolished the ability of OMZ175 to bind to collagen and laminin and invade HCAECs, and significantly protected G. mellonella against OMZ175 infection. We concluded that neither CnaB nor CbpA are necessary for the expression of Cnm-related traits. We also provided definitive evidence that Cnm is an important virulence factor and a suitable target for the development of novel preventive and therapeutic strategies to combat invasive S. mutans strains. This article is protected by copyright. All rights reserved.
    Full-text · Article · Sep 2013
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    • "This protein was shown to be highly homologous to the collagen-binding protein of Staphylococcus aureus, Cna, which plays an important role in the animal model of IE (Hienz et al., 1996). This aspect was also emphasized by the finding that the collagenbinding abilities of strains with the cnm gene were significantly greater than those of strains without the gene (Nomura et al., 2009). In addition, the Cnm protein was proved to be necessary for invasion of human coronary artery endothelial cells (Abranches et al., 2011). "
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    ABSTRACT: Streptococcus mutans is one of the oral pathogens associated with infective endocarditis (IE). With respect to bacterial binding ability to the extracellular matrix, the Cnm protein, a cell surface collagen-binding adhesin of S. mutans, is known as one of the possible virulence factors with regard to IE. In this study, we aimed to determine the distribution of the cnm gene, which encodes Cnm, in a large number of clinical isolates of S. mutans from Thai subjects. Then, the cnm-positive strains were classified using a multilocus sequence typing (MLST) scheme, which we constructed previously. In addition, the data were analysed together with our previous MLST data of cnm-positive strains from Japan and Finland in order to evaluate the clonal relationship among S. mutans strains harbouring the cnm gene. The cnm gene was detected in 12.4 % of all 750 Thai isolates, and serotype f showed the highest rate of detection (54.5 %). According to the MLST data, two clonal complex groups were revealed as the important clones related to cnm-positive S. mutans from various origins of isolation. Moreover, the collagen-binding properties of S. mutans strains with the cnm gene were significantly greater than those of strains without the gene, although four cnm-negative strains classified into two sequence types (STs), ST110 and ST136, showed extremely high collagen-binding rates suggesting the presence of additional genes involved with collagen binding in these STs. Taken together, these results provided information on both epidemiological as well as evolutional aspects of S. mutans possessing the cnm gene.
    Preview · Article · Jun 2011 · Journal of Medical Microbiology
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    ABSTRACT: Streptococcus mutans, generally known as a major pathogen of dental caries, is also a possible causative agent of bacteremia and infective endocarditis. S. mutans is classified into serotypes c, e, f and k based on the chemical composition of serotype-specific polysaccharides, with approximately 70-80% of strains found in the oral cavity classified as serotype c, followed by e (approximately 20%), and f and k (less than 5% each). Serotype k was recently designated as a novel serotype and shown to possess unique features, the most prominent being a defect of the glucose side chain in serotype-specific rhamnose-glucose polymers, which is related to a higher incidence of detection in cardiovascular specimens, owing to phagocytosis resistance. Molecular analyses of cardiovascular specimens showed a high detection frequency for S. mutans DNA, among which the detection rate for serotype k was quite high. These findings suggest that serotype k S. mutans possibly has a high level of virulence for systemic diseases.
    No preview · Article · Oct 2009 · Future Microbiology
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