The alpha subunits of Francisella tularensis RNA polymerase

描述(申请人提供)：图拉氏方济氏菌是图拉热症的病原体，是目前已知的最具传染性的细菌病原体之一，也是一种潜在的生物武器。它既是一种环境有机体，也是一种病原体，因此必须在变化很大的条件下生存。然而，令人惊讶的是，图拉藻编码的转录调节因子相对较少。对图拉氏丝虫基因组序列的检查发现了两个基因，命名为rpoA1和rpoA2，编码不同的RNA聚合酶a亚单位(Rnap)。这种情况是史无前例的；在迄今为止测序的所有其他细菌基因组中，只有一个rpoA基因。由于a通过直接序列特异的蛋白质-DNA相互作用参与启动子识别，并且a是转录激活剂的共同靶标，因此a含量不同的RNAP分子可能具有非常不同的性质。在这里，我们建议采用遗传和生化方法相结合的方法来确定图拉藻中的RNAP是否包含两个功能不同的a亚基。这些研究将对如何控制图拉氏丝虫的基因表达具有重要意义；使用具有不同a亚基的RNAP群体可能代表识别不同类别启动子和控制转录的独特策略，这一策略可能被用于设计专门针对图拉氏丝虫的抗菌剂。

DESCRIPTION (provided by applicant): Francisella tularensis, the aetiological agent of tularemia, is one of the most infectious bacterial pathogens currently known and a potential biological weapon. It is both an environmental organism and a pathogen, and must therefore survive under widely varying conditions. Strikingly, however, F. tularensis encodes relatively few transcription regulators. Inspection of the F. tularensis genome sequence reveals two genes, designated rpoA1 and rpoA2, encoding different a subunits of RNA polymerase (RNAP). This situation is without precedent; in all other bacterial genomes sequenced to date there is only one rpoA gene. Because a participates in promoter recognition through direct sequence-specific protein-DNA interactions, and because a is a common target for transcription activators, RNAP molecules that differ from one another with respect to their a content may have very different properties. Here we propose to take a combination of genetic and biochemical approaches to determine whether or not RNAP in F. tularensis contains two functionally distinct a subunits. These studies will have important implications for how gene expression is controlled in F. tularensis; the use of an RNAP population with different a subunits may represent a unique strategy for recognizing different classes of promoter and controlling transcription, one that might be exploited in the design of antimicrobials that specifically target F. tularensis.