Contribution of biofilm regulatory protein A of Streptococcus mutans, to systemic virulence

Contribution of biofilm regulatory protein A of Streptococcus mutans, to systemic virulence
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DOI:
10.1016/j.micinf.2005.04.012
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发表时间:
2005-08-01
影响因子:
5.8
通讯作者:
Ooshima, T
Ooshima, T
中科院分区:
医学3区
文献类型:
--
作者:
Nakano, K;Fujita, K;Ooshima, T

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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,并讨论了它可能是这些疾病的病因的可能性。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期存活。最近,对编码变形链球菌生物膜调节蛋白A(BrPA)的brPA基因进行了克隆和测序,结果表明,同基因突变株的brPA失活导致链形成比亲本株更长。本研究从菌株MT8148出发,构建了一株BrPA缺陷型等基因突变株MT8148BRD。在对MT814813RD吞噬人多形核白细胞(PMN)的敏感性分析中,MT814813RD的吞噬效率明显低于MT8148(P<0.01)。其次,在不同初始pH条件下对MT8148进行培养,得到不同链长的菌株,发现吞噬敏感性与链长呈显著负相关(P&lt;0.01)。此外,MT8148BRD比MT8148具有更高的血小板聚集性(P&lt;0.05)。此外,将MT8148BRD注射到无特定病原体的Spraogue-Dawley大鼠的颈静脉会导致更长的菌血症持续时间,与感染MT8148的大鼠相比,这会延长全身炎症的时间。这些结果表明,变形链球菌BrPA与血液中的毒力有关,因为它与吞噬敏感性和血小板聚集特性有关。(C)2005年爱思唯尔集团。版权所有。
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 MT814813RD 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. (c) 2005 Elsevier SAS. All rights reserved.