Molecular analysis of cell surface structures of Streptococcus mutans for virulence of infective endocarditis

变形链球菌细胞表面结构对感染性心内膜炎毒力的分子分析

• 批准号: 16390605
• 负责人: OOSHIMA Takashi
• 金额: $ 9.09万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390605/
• 关键词: infective endocarditis; Streptococcus mutants; heart valve; vegetation; dental plaque; PCR; serotype; グルコシルトランスフェラー; 血清型特異多糖抗原; Protein antigen c; 多型核白血球; 貪食作用; 食作用

The unserotypeable Streptococcus mutants strains isolated from blood of the patients with infective endocarditis was designated as novel serotype k. The serotype k strains is featured with the drastic reduction of the glucose side chains attached to the rhamnose backbone in the serotype-specific polysaccharide. The serotype k strains were shown to be generally less cariogenic, while they induced longer duration of bacteremia due to the resistance to phagocytosis by polymorphonuclear leukocytes. The genes involved with the biosynthesis of serotype-specific polysaccharide were sequenced, which revealed the existence of the specific region common in serotype k strains. Using the nucleotides of this region, the PCR method for rapid identification of the subjects with serotype k strains was constructed.The isogenic mutant strains with the defect of major surface antigens of S. mutants were generated by insertional inactivation of the genes encoding each protein. The in vitro and rat bacteremia model experiments showed that protein antigen (PA) and glucan-binding protein C (GbpC) were involved with the virulence of S. mutants in blood. In addition, inactivation of the biofilm regulatory protein A (BrpA) resulted in the longer chain formation, which enhanced the platelet aggregation properties.PCR detection of oral bacteria using the DNA extracted from heart valve and athermatous plaque specimens extirpated in the cardiovascular operations has been carried out. The bacterial species involved with periodontitis was identified, however, the detection rate of S. mutants was extremely higher than these species. Furthermore, the serotype distribution of S. mutants in cardiovascular specimens was shown to be totally different from that in the oral cavity. These results indicate that S. mutants is possibly associated with the cardiovascular diseases.

从感染性心内膜炎患者血液中分离出的不可血清型链球菌突变株被命名为新血清型k。血清型k菌株的特点是血清型特异性多糖中连接至鼠李糖主链的葡萄糖侧链急剧减少。 k血清型菌株通常致龋性较低，但由于多形核白细胞对吞噬作用的抵抗力，它们会诱导较长时间的菌血症。对涉及血清型特异性多糖生物合成的基因进行了测序，揭示了血清型 k 菌株中常见的特定区域的存在。利用该区域的核苷酸，构建了快速鉴定k血清型菌株的PCR方法。通过插入失活编码各蛋白的基因，产生了具有S.突变体主要表面抗原缺陷的等基因突变株。体外和大鼠菌血症模型实验表明，蛋白抗原（PA）和葡聚糖结合蛋白C（GbpC）与S.突变体在血液中的毒力有关。此外，生物膜调节蛋白A（BrpA）的失活导致了更长的链形成，从而增强了血小板聚集特性。使用从心血管手术中摘除的心脏瓣膜和动脉粥样斑块标本中提取的DNA对口腔细菌进行了PCR检测。与牙周炎相关的细菌种类已被鉴定，但 S. 突变体的检出率远高于这些种类。此外，心血管标本中S.突变体的血清型分布与口腔中的血清型分布完全不同。这些结果表明S.突变体可能与心血管疾病有关。

项目成果

Detection of cariogenic Streptococcus mutans in extirpated heart valve and atheromatous plaque specimens

• DOI: 10.1128/jcm.00377-06
• 发表时间: 2006-09-01
• 期刊: JOURNAL OF CLINICAL MICROBIOLOGY
• 影响因子: 9.4
• 作者: Nakano, Kazuhiko;Inaba, Hiroaki;Ooshima, Takashi
• 通讯作者: Ooshima, Takashi

Demonstration of Streptococcus mutans with a cell wall polysaccharide specific to a new serotype, k, in the human oral cavity

• DOI: 10.1128/jcm.42.1.198-202.2004
• 发表时间: 2004-01-01
• 期刊: JOURNAL OF CLINICAL MICROBIOLOGY
• 影响因子: 9.4
• 作者: Nakano, K;Nomura, R;Ooshima, T
• 通讯作者: Ooshima, T

Serotype distribution of Streptococcus mutans, a pathogen of dental caries, in cardiovascular specimens from Japanese patients

日本患者心血管标本中龋齿病原体变形链球菌的血清型分布

• 发表时间: 2007
• 期刊: J Med Microbiol 56
• 作者: Nakano K;Nemoto H;Nomura R;Homma H;Yoshioka H;Shudo Y;Hata H;Toda K;Taniguchi K;Amano A;Ooshima T
• 通讯作者: Ooshima T

Development of a polymerase chain reaction method for rapid identification of new Streptococcus mutans serotype k strains.

开发用于快速鉴定新的变形链球菌 k 血清型菌株的聚合酶链反应方法。

• 发表时间: 2004
• 期刊: Journal of Clinical Microbiology 49・11
• 作者: Nomura R;et al.;Nakano K et al.;Nomura R et al.;Nakano K et al.
• 通讯作者: Nakano K et al.

Demonstration of Streptococcus mutants with a cell wall polysaccharide specific to a new serotype, k, in the human oral cavity.

在人类口腔中展示具有针对新血清型 k 的细胞壁多糖的链球菌突变体。

• 发表时间: 2004
• 期刊: Journal of Clinical Microbiology 42
• 作者: Nomura R;et al.;Nakano K et al.;Nomura R et al.;Nakano K et al.;Nakano K et al.
• 通讯作者: Nakano K et al.