Nakano Kazuhiko, Fujita Kazuyo, Nishimura Kaoru, Nomura Ryota, Ooshima Takashi
Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, 1-8 Yamada-oka, Suita, Osaka 565-0871, Japan.
Microbes Infect. 2005 Aug-Sep;7(11-12):1246-55. doi: 10.1016/j.micinf.2005.04.012. Epub 2005 Jun 8.
Streptococcus mutans is occasionally isolated from the blood of patients with bacteremia and infective endocarditis (IE), and the possibility that it could be pathogenic for those diseases has been discussed. The initial important step for the involvement of bacterial pathogens in the virulence of IE is thought to be survival in blood for an extended period. Recently, the brpA gene encoding biofilm regulatory protein A (BrpA) of S. mutans was cloned and sequenced, after which it was shown that inactivation of brpA in an isogenic mutant strain resulted in longer chain formation than in the parental strain. In the present study, a BrpA-defective isogenic mutant strain (MT8148BRD) was constructed from strain MT8148. In an analysis of its susceptibility to phagocytosis by human polymorphonuclear leukocytes (PMNs), the phagocytosis rate of MT8148BRD was shown to be significantly lower than that of MT8148 (P < 0.01). Next, strains with various chain lengths were produced by culturing MT8148 in media with various initial pH levels, which revealed that there was a statistically negative correlation between phagocytosis susceptibility and chain length (P < 0.01). Further, MT8148BRD was found to possess higher platelet aggregation properties than MT8148 (P < 0.05). In addition, injection of MT8148BRD into the jugular vein of specific pathogen-free Sprague-Dawley rats resulted in a longer duration of bacteremia, which prolonged systemic inflammation for a longer period than in those infected with MT8148. These results indicate that S. mutans BrpA is associated with virulence in blood, due to its correlation to phagocytosis susceptibility and platelet aggregation properties.
变形链球菌偶尔会从菌血症和感染性心内膜炎（IE）患者的血液中分离出来，并且人们已经讨论了它可能对这些疾病具有致病性的可能性。细菌病原体参与IE毒力的最初重要步骤被认为是在血液中长时间存活。最近，编码变形链球菌生物膜调节蛋白A（BrpA）的brpA基因被克隆并测序，之后表明在同基因突变菌株中brpA的失活导致比亲本菌株形成更长的链。在本研究中，从MT8148菌株构建了BrpA缺陷的同基因突变菌株（MT8148BRD）。在分析其对人多形核白细胞（PMN）吞噬作用的敏感性时，MT8148BRD的吞噬率显示显著低于MT8148（P < 0.01）。接下来，通过在具有不同初始pH水平的培养基中培养MT8148产生了具有不同链长度的菌株，这表明吞噬易感性与链长度之间存在统计学上的负相关（P < 0.01）。此外，发现MT8148BRD比MT8148具有更高的血小板聚集特性（P < 0.05）。另外，将MT8148BRD注射到无特定病原体的Sprague-Dawley大鼠的颈静脉中导致菌血症持续时间更长，与感染MT8148的大鼠相比，全身炎症持续的时间更长。这些结果表明，变形链球菌BrpA与血液中的毒力相关，因为它与吞噬易感性和血小板聚集特性相关。
