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首页> 外文期刊>Infection and immunity >Expression of the Type 1 Pneumococcal Pilus Is Bistable and Negatively Regulated by the Structural Component RrgA
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Expression of the Type 1 Pneumococcal Pilus Is Bistable and Negatively Regulated by the Structural Component RrgA

机译：1型肺炎球菌毛囊的表达是双稳态的，并且受结构成分RrgA的负调控。

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The pneumococcal type 1 pilus, which is present in 25 to 30% of clinical isolates, has been associated with increased adherence and inflammatory responses and is being evaluated as a potential vaccine candidate. Here we show that expression of the pilus is bistable as a result of the molecular interaction between the transcription activator RrlA and a structural component of the pilus called RrgA. Sampling various clinical pneumococcal isolates that harbor the type 1 pilus-encoding islet, we show that distinct populations of cells can be identified with either undetectable or prominent pilus expression. When these two populations are separated and regrown in liquid medium, they are phenotypically different: the nonexpressing population reverts to the previous bimodal distribution, whereas the expressing population retains the same high level of pilus expression. Controlled exogenous expression of the regulatory pilus gene rlrA in a strain from which the endogenous version has been deleted increases pilus expression steadily, suggesting that the bistable expression of the pilus observed in wild-type cells is dependent on the native rlrA promoter. Finally, we demonstrate that RrgA is a negative regulator of pilus expression and that this repression is likely mediated through direct interaction with RlrA. We conclude that type 1 pilus expression in pneumococcus exhibits a bistable phenotype, which is dependent upon the molecular interplay between the RlrA and RrgA proteins. We suggest that this flexibility in expression may assist adaptation to a range of immune conditions, such as evasion of antipilus antibodies, within potential hosts.
机译：肺炎球菌1型菌毛存在于25％至30％的临床分离株中，与依从性和炎症反应增加有关，正在被评估为潜在的疫苗候选者。在这里，我们显示菌毛的表达是双稳态的，这是转录激活因子RrlA与菌毛的称为RrgA的结构成分之间发生分子相互作用的结果。采样各种具有1型菌毛编码胰岛的临床肺炎球菌分离株，我们显示出可以检测到具有不可检测或显着菌毛表达的不同细胞群。当这两个种群分离并在液体培养基中再生时，它们在表型上是不同的：非表达种群恢复为先前的双峰分布，而表达种群则保持相同的高菌毛表达水平。在已删除内源版本的菌株中，调节菌毛基因 rlrA 的受控外源表达稳定地增加了菌毛的表达，这表明在野生型细胞中观察到的菌毛的双稳态表达依赖于天然的 rlrA 启动子。最后，我们证明RrgA是菌毛表达的负调节剂，并且这种抑制可能是通过与RlrA的直接相互作用介导的。我们得出结论，肺炎球菌中的1型菌毛表达表现出双稳态表型，这取决于RlrA和RrgA蛋白之间的分子相互作用。我们建议这种表达的灵活性可能有助于适应潜在宿主内的一系列免疫条件，例如逃避抗菌毛抗体。

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