Systematic Functional Analysis Reveals That a Set of Seven Genes Is Involved in Fine-Tuning of the Multiple Functions Mediated by Type IV Pili in Neisseria meningitidis
Systematic Functional Analysis Reveals That a Set of Seven Genes Is Involved in Fine-Tuning of the Multiple Functions Mediated by Type IV Pili in Neisseria meningitidis
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DOI：
10.1128/iai.00099-10
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发表时间：
2010-07-01
影响因子：
3.1
通讯作者：
Pelicic, Vladimir
中科院分区：
文献类型：
--
作者：
Brown, Daniel R.;Helaine, Sophie;Pelicic, Vladimir
IV型菌毛（Tfp）介导多种表型，从粘附到运动，是细菌中最广泛的毒力因子之一。然而，Tfp生物发生的分子机制及其相关功能仍然知之甚少。其中一个潜在的原因是，Tfp生物学中涉及的众多基因所起的作用尚不清楚，因为相应的突变是在个案基础上，在不同的物种中，使用不同的检测方法进行研究的，通常会产生不同的结果。因此，我们最近开始了一项系统的功能分析，涉及人类病原体脑膜炎奈瑟菌临床分离的Tfp生物学基因。在先前研究了16个参与Tfp生物发生的基因后，我们在这里报道了7个基因的特征，这些基因在pphilip中是必不可少的，并且可能参与Tfp生物学。通过一系列的实验，我们评估了单突变体、双突变体（其中纤维收缩被pilT的并发突变消除）和过表达相应蛋白质的菌株的pilip和每个tfp连接的功能。这表明，七个基因中的每一个实际上都微调了与Tfp相关的功能，这使我们更接近于了解脑膜炎球菌中Tfp生物学的全局视图。
Type IV pili (Tfp), which mediate multiple phenotypes ranging from adhesion to motility, are one of the most widespread virulence factors in bacteria. However, the molecular mechanisms of Tfp biogenesis and associated functions remain poorly understood. One of the underlying reasons is that the roles played by the numerous genes involved in Tfp biology are unclear because corresponding mutants have been studied on a case-by-case basis, in different species, and using different assays, often generating heterogeneous results. Therefore, we have recently started a systematic functional analysis of the genes involved in Tfp biology in a well-characterized clinical isolate of the human pathogen Neisseria meningitidis. After previously studying 16 genes involved in Tfp biogenesis, here we report the characterization of 7 genes that are dispensable for piliation and potentially involved in Tfp biology. Using a battery of assays, we assessed piliation and each of the Tfp-linked functions in single mutants, double mutants in which filament retraction is abolished by a concurrent mutation in pilT, and strains overexpressing the corresponding proteins. This showed that each of the seven genes actually fine-tunes a Tfp-linked function(s), which brings us one step closer to a global view of Tfp biology in the meningococcus.