Pseudomonas Global Regulatory Networks in Biofilms

随着我们获得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，我们对细菌在任何环境中生长的看法正在发生变化。也许微生物群落最有趣的方面是细菌可以交流和协调它们的反应，使它们以类似于简单多细胞生物的方式运作。细菌通过一种称为全球调控网络的系统来控制这些群体行为。这些系统允许细菌群体感知、响应、交流和协调它们的反应。我们感兴趣的是三个全球性的监管系统：严格的反应，使细胞能够感知和响应营养限制;群体感应，使细菌能够感知他们的邻居，响应和协调人口;和GacA/S两个组件系统参与生物膜的形成和维护。这项研究的目的是了解这三个系统如何在细菌生物膜中协同工作。为了进行这项研究，我们将使用一种名为铜绿假单胞菌的细菌，以其形成生物膜的能力及其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，特别是寻找至少在两个系统中重叠的基因。我们将在全局调节系统中使用突变体来研究它们对其他系统的影响。例如，我们将使用突变体在严格的反应，以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疗法的目标的发展。

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.