Pseudomonas Global Regulatory Networks in Biofilms

我们对细菌在任何环境中生长的看法正在改变，因为我们获得了更多关于细菌如何作为微生物群落（称为生物膜）生长的信息。也许微生物群落最有趣的方面是，细菌可以沟通和协调它们的反应，使它们以一种类似于简单的多细胞生物的方式运作。细菌通过称为全球调节网络的系统来控制这些社区行为。这些系统允许细菌群体感知、反应、交流和协调它们的反应。我们对三种全球调控系统感兴趣：允许细胞感知和响应营养限制的严格反应；群体感应（Quorum sensing）——细菌可以感应到它们的邻居，做出反应并协调群体；参与生物膜形成和维持的GacA/S双组分系统。这项研究的目的是了解这三个系统是如何在细菌生物膜中协同工作的。为了进行这项研究，我们将使用一种叫做铜绿假单胞菌的细菌，这种细菌以其形成生物膜的能力和在生物膜感染中的作用而闻名。我们将研究这些系统诱导和抑制的基因，特别是寻找至少两个系统中重叠的基因。我们将使用全球监管系统中的突变体来检查它们对其他系统的影响。例如，我们将在严格响应中使用突变体来检查它们对群体感应和GacA/S系统的影响。最后，我们将研究每个全球调控系统在抗生素耐药性中的作用及其在细菌应激反应中的总体作用。这项研究将使我们更好地了解细菌如何形成细菌群落，并可能导致新的抗菌治疗靶点的发展。

Our view of bacteria growing in any environment is changing as we gain more information on how bacteria grow as microbial communities, called biofilms. Perhaps the most interesting aspect of microbial communities is that the bacteria can communicate and coordinate their responses such that they operate in a manner similar to simple multicellular organisms. Bacteria control these community behaviours using systems called global regulatory networks. These systems allow the bacterial population to sense, respond, communicate and coordinate their responses. We are interested in three global regulatory systems: the stringent response which allows cells to sense and respond to nutrient limitation; quorum sensing which allows bacteria to sense their neighbours, respond and coordinate the population; and the GacA/S two component system involved in biofilm formation and maintenance. The goal of this research is to understand how these three systems work together in a bacterial biofilm. To carry out this research we will use a bacterium called Pseudomonas aeruginosa, known for its ability to form biofilms and its role in biofilm infections. We will examine the genes induced and repressed by these systems and in particular look for genes that overlap in at least two of these systems. We will use mutants in the global regulatory systems to examine their effect on the other systems. For instance we will use mutants in the stringent response to examine their effects on quorum sensing and the GacA/S system. Finally, we will examine the role of each of the global regulatory systems in the antibiotic resistance and their overall role in bacterial stress responses. This research will give us a better understanding of how bacteria form bacterial communities and potentially lead to the development of targets for new antibacterial therapies.