Novel transcriptional regulators of virulence in the genus Burkholderia

细菌已经进化出系统，通过这些系统它们可以感知环境，使它们能够根据环境条件打开和关闭基因，从而确保它们继续生存和成功。一类这样的传感器是双组分系统(TCS)家族。双组分系统由细菌表面的传感器蛋白组成，该传感器蛋白检测特定信号的存在，并将该信号传递给蛋白质(称为反应调节器)。在细菌内部。然后，反应调节器打开或关闭各种基因，使细菌能够对原始信号做出反应。这些TC可以启动细菌致病所必需的不同基因。在某些情况下，缺乏特定TCS的细菌根本不会致病，可以用作疫苗。这项研究将调查一组名为伯克霍尔德氏菌的细菌中的TCS。这些细菌对几乎所有可用的抗生素都有抗药性，能够引起人类、动植物的严重疾病。伯克霍尔德氏菌群中的两个特定物种可以用作战剂。与之形成鲜明对比的是，其他伯克霍尔德氏菌是居住在土壤中的无害细菌，在那里它们可以提高作物产量，从而导致它们在环境中应用的呼声。伯克霍尔德氏菌是如何控制这种非凡的多样性的尚不清楚。从现有的基因组序列来看，很明显伯克霍尔德氏菌拥有异常多的TCS。初步研究表明，伯克霍尔德氏菌中的TCS与其他细菌物种中的同等系统的行为非常不同。这项拟议的研究将调查这些新的伯克霍尔德菌TCS，并确定那些对致病特别重要的TCS。在确定了这些关键的TC之后，将进行研究，以揭示这些系统正在开启或关闭哪些基因。不同的伯克霍尔德氏菌在致病能力上有很大的不同。可以和不能引起疾病的伯克霍尔德氏菌的基因组序列将被比较，看看这些不同的能力是否可以通过特定的TCS及其相关基因的存在或不存在来解释。最后，TCS抑制剂将针对伯克霍尔德氏菌进行测试，以确定此类抑制剂是否可用作新的抗生素。总之，这项研究将确定对致病至关重要的伯克霍尔德氏菌系统，从而确定治疗和预防伯克霍尔德氏菌感染的新方法。

Bacteria have evolved systems through which they can sense their environment, enabling them to turn genes on and off in response to environmental conditions and thus ensure their continued survival and success. One such class of sensors is the family of two-component systems (TCSs). Two-component systems comprise a sensor protein on the bacterial surface that detects the presence of a particular signal and relays that signal to a protein (termed the ?response regulator?) inside the bacteria. The response regulator then turns a variety of genes on or off, enabling the bacteria to respond to the original signal. These TCSs can switch on diverse genes that are necessary for the bacteria to cause disease. In some cases, bacteria which lack a particular TCS cannot cause disease at all, and can be used as a vaccine. This study will investigate the TCSs within a group of bacteria called Burkholderia. These bacteria are resistant to almost every available antibiotic and are capable of causing serious disease of humans, animals and plants. Two particular species within the Burkholderia group can be used as warfare agents. In stark contrast, other Burkholderia are harmless bacteria residing in soil where they can boost crop production, resulting in calls for their environmental application. How Burkholderia organisms control this remarkable diversity is unknown. From available genome sequences, it is apparent that Burkholderia organisms possess an unusually high number of TCSs. Preliminary studies show that the TCSs within Burkholderia behave very differently from equivalent systems within other bacterial species. The proposed research will investigate these novel Burkholderia TCSs, and identify those which are particularly important for causing disease. Having identified these key TCSs, studies will be performed that will reveal which genes are being turned on or off by these systems. Different Burkholderia species vary considerably in their ability to cause disease. Genome sequences of Burkholderia that can and cannot cause disease will be compared to see if these differing abilities might be explained by the presence or absence of particular TCSs and their associated genes. Finally, TCS inhibitors will be tested against Burkholderia to determine whether such inhibitors may be used as novel antibiotics. In conclusion, this research will identify Burkholderia systems that are essential for causing disease, thus identifying novel ways to treat and prevent Burkholderia infection.