Ghosh Pritha, Sowdhamini Ramanathan
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore, Karnataka, 560 065, India.
BMC Genomics. 2017 Aug 24;18(1):658. doi: 10.1186/s12864-017-4045-3.
Pathogenic bacteria have evolved various strategies to counteract host defences. They are also exposed to environments that are undergoing constant changes. Hence, in order to survive, bacteria must adapt themselves to the changing environmental conditions by performing regulations at the transcriptional and/or post-transcriptional levels. Roles of RNA-binding proteins (RBPs) as virulence factors have been very well studied. Here, we have used a sequence search-based method to compare and contrast the proteomes of 16 pathogenic and three non-pathogenic E. coli strains as well as to obtain a global picture of the RBP landscape (RBPome) in E. coli.
Our results show that there are no significant differences in the percentage of RBPs encoded by the pathogenic and the non-pathogenic E. coli strains. The differences in the types of Pfam domains as well as Pfam RNA-binding domains, encoded by these two classes of E. coli strains, are also insignificant. The complete and distinct RBPome of E. coli has been established by studying all known E. coli strains till date. We have also identified RBPs that are exclusive to pathogenic strains, and most of them can be exploited as drug targets since they appear to be non-homologous to their human host proteins. Many of these pathogen-specific proteins were uncharacterised and their identities could be resolved on the basis of sequence homology searches with known proteins. Detailed structural modelling, molecular dynamics simulations and sequence comparisons have been pursued for selected examples to understand differences in stability and RNA-binding.
The approach used in this paper to cross-compare proteomes of pathogenic and non-pathogenic strains may also be extended to other bacterial or even eukaryotic proteomes to understand interesting differences in their RBPomes. The pathogen-specific RBPs reported in this study, may also be taken up further for clinical trials and/or experimental validations.
致病细菌已经进化出各种策略来对抗宿主防御。它们也暴露于不断变化的环境中。因此，为了生存，细菌必须通过在转录和/或转录后水平进行调控来使自身适应不断变化的环境条件。RNA结合蛋白（RBPs）作为毒力因子的作用已经得到了很好的研究。在这里，我们使用了一种基于序列搜索的方法来比较和对比16种致病性大肠杆菌菌株和3种非致病性大肠杆菌菌株的蛋白质组，以及获得大肠杆菌中RBP图谱（RBPome）的全局图景。
我们的结果表明，致病性和非致病性大肠杆菌菌株编码的RBPs百分比没有显著差异。这两类大肠杆菌菌株编码的Pfam结构域以及Pfam RNA结合结构域类型的差异也不显著。通过研究迄今为止所有已知的大肠杆菌菌株，已经建立了完整且独特的大肠杆菌RBPome。我们还鉴定出了致病性菌株特有的RBPs，其中大多数可以用作药物靶点，因为它们似乎与人类宿主蛋白没有同源性。这些病原体特异性蛋白中有许多尚未被表征，它们的身份可以通过与已知蛋白的序列同源性搜索来确定。对于选定的例子，已经进行了详细的结构建模、分子动力学模拟和序列比较，以了解稳定性和RNA结合方面的差异。
本文中用于交叉比较致病性和非致病性菌株蛋白质组的方法也可以扩展到其他细菌甚至真核生物蛋白质组，以了解它们RBPomes中有趣的差异。本研究中报道的病原体特异性RBPs也可能会进一步用于临床试验和/或实验验证。
