Characterisation of a sigma factor with an on-board iron-responsive regulatory domain

伯克霍尔德氏菌是一组不同的细菌，它们生活在环境中，特别是土壤中，并与植物相关。它们之所以重要，原因有很多。首先，它们具有代谢多种化学物质的能力，这使它们在污染环境的生物修复和解毒方面具有潜在的实用价值。它们也是各种有趣的化合物的来源，这些化合物具有医学或药理上的重要性。一些物种是植物病原体(导致植物疾病)，而另一些物种则用于保护植物免受各种微生物病原体的侵袭，从而提高作物的生长产量。近几十年来，由于这一群体中的一些成员有能力在人和动物中造成严重感染，它们变得突出起来。由于伯克霍尔德氏菌表现出高度的抗药性，这类感染极难治疗。与大多数生物一样，伯克霍尔德氏菌需要铁来生长，它们拥有从环境和人类宿主获得铁的非常有效的机制。因此，伯克霍尔德氏菌的铁获取系统可能成为未来针对这些细菌的药物开发的靶点。它们还可以作为控制植物致病或促进植物生长的伯克霍尔德氏菌生长的手段。为此，我们正在研究这类细菌摄取铁的机制及其调节。我们已经确定了一种独特的机制，一些伯克霍尔德氏菌通过这种机制感知环境中的铁并对其做出反应。具体地说，由一种被称为西格玛因子的蛋白质组成的特定调控元件，针对特定的基因组进行表达，是唯一能够直接对铁做出反应的元件。这个项目的目的是应用一系列分子方法来研究这种西格玛因子能够感知铁并对其做出反应的机制。从这项研究中获得的信息将使人们能够更好地了解细菌中的基因表达和调控，并可能成为制定干预策略的跳板，以控制伯克霍尔德氏菌在环境中或在动物和人类宿主中的生长。

The Burkholderia are a diverse group of bacteria that live in the environment, particularly in the soil and in association with plants. They are important for a number of reasons. First, they have the ability to metabolise a wide variety of chemicals, and this makes them potentially useful in bioremediation and detoxification of contaminated environments. They are also the source of a variety of interesting compounds that have medical or pharmacological importance. Several species are phytopathogenic (cause disease in plants) while others serve to protect plants from a variety of microbial pathogens and thereby increase the growth yield of crop plants. In recent decades they have come to prominence by virtue of the ability of some members of this group to cause serious infections in humans and animals. Such infections are extremely difficult to treat due to the high level of antibiotic resistance exhibited by Burkholderia.As with the majority of living things, Burkholderia require iron to grow and they possess very efficient mechanisms to obtain iron from the environment and from the human host. Therefore, the iron acquisition systems of Burkholderia may serve as a target for future development of drugs to target these bacteria. They may also serve as a means for controlling the growth of plant pathogenic or plant growth-promoting Burkholderia. To this end, we are investigating the mechanisms of iron uptake and its regulation in this group of bacteria. We have identified a unique mechanism by which some species of Burkholderia sense and respond to iron in the environment. Specifically, a particular regulatory element consisting of a protein, known as a sigma factor, that targets particular sets of genes for expression is uniquely able to respond to iron directly. The purpose of this project is to apply a range of molecular approaches to investigate the mechanism by which this sigma factor is able to sense and respond to iron. The information gained from this study will permit a greater understanding of gene expression and regulation in bacteria and may serve as a springboard for the development of intervention strategies to control the growth of Burkholderia either in the environment or in animal and human hosts.