Riboregulation in periodontopathogen Porphyromonas gingivalis

牙周病原菌牙龈卟啉单胞菌的核糖调节

• 批准号: 8781820
• 负责人: Janina P Lewis
• 金额: $ 22.88万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-03 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8781820
• 关键词: Affect; Anaerobic Bacteria; Bacteria; Bacteroides; Bacteroides fragilis; Bacteroides thetaiotaomicron; Binding; Bioinformatics; Body part; Capnocytophaga; Cardiovascular system; Cells; Complex; Data; Data Analyses; Development; Distant; Environment; Gene Expression Profile; Gene Proteins; Genes; Gram-Negative Anaerobic Bacteria; Heart; In Vitro; Invaded; Investigation; Lead; Light; Mediating; Messenger RNA; Molecular Chaperones; Oral; Oral cavity; Organism; Periodontal Diseases; Periodontal Pocket; Play; Porphyromonas gingivalis; Post-Transcriptional Regulation; Precipitation; Prevotella intermedia; Process; Proteins; Proteome; RNA; RNA Binding; RNA-Binding Proteins; Regulation; Regulatory Pathway; Role; Route; Specificity; Staging; Therapeutic Agents; Tissues; Virulence; Work; antimicrobial; base; design; environmental change; insight; mutant; nitrosative stress; novel; pathogen; periodontopathogen; protein expression; public health relevance; response

DESCRIPTION (provided by applicant): Porphyromonasgingivalis, a gram-negative anaerobic bacterium, is a recognized periodontopathogen. Although it mainly inhabits anaerobic periodontal pockets it also is present in other niches of the oral cavity enroute to the periodonta pockets as well as it can access distant parts of the body such as cardiovascular system and heart tissues. Finally, it can invade and survive within host cells. In order to adapt to the varios niches the organism is expected to have efficient regulatory mechanisms allowing it to rapidly alter gene and ultimately protein expression in response to the various challenges imposed by the host environments. Riboregulation has emerged as a significant mechanism of post-transciptional regulation in bacteria. The RNA chaperone, Hfq, has been shown to play an indispensable role in this process by binding sRNAs and stabilizing the sRNA-mRNA duplexes. However, at least 50% of bacteria lack Hfq indicating the presence of other novel mechanisms mediating sRNA regulation. Using bioinformatics approaches we identified a candidate for an RNA-binding protein, designated here as Pgr, in P.gingivalis. Our preliminary data demonstrate that the protein binds RNA and plays a role in survival of the bacterium with nitrosative stress as well as in the presence of host cells. Furthermore, we noted significant changes in RNA levels resulting from deletion of Pgr. Based on the preliminary data we hypothesize that Pgr is a novel RNA chaperone and plays a major role in post-transcriptional regulation in P. gingivalis. As Pgr function is relevant for full virulence of the bacterium, it will serve as an excellent target for development of antimicrobial strategies. To gain an insight into the mechanism of regulation by the protein we will define the transcriptome and proteome affected by the absence of the protein as well as identify the RNAs interacting with Pgr. We expect that once completed this work will provide insight into mechanism of action of this protein and ultimately will lead to design of strategies interfering with its action and thus reducing virulence of P. gingivalis. Finally, we predict that this work will shed light on the mechanisms of riboregulation in other Bacteroides- related bacteria such as Prevotella intermedia, Tannerella forsythensis, Bacteroides fragilis, B. thetaiotaomicron and Capnocytophaga hutchinsonii.

描述（由申请人提供）：卟啉症，一种革兰氏阴性厌氧菌细菌，是公认的牙周病原。尽管它主要居住在厌氧牙周口袋中，但在口腔的其他壁ni中也存在于周期口袋，并且可以进入人体遥远的部分，例如心血管系统和心脏组织。最后，它可以入侵并在宿主细胞内生存。为了适应Varios生态生物，有预计有效的调节机制，使其能够快速改变基因，并最终响应宿主环境所面临的各种挑战。核糖调节已成为细菌递交后调节的重要机制。 RNA伴侣HFQ已被证明通过结合SRNA并稳定SRNA-MRNA双链体在此过程中起着必不可少的作用。然而，至少50％的细菌缺乏HFQ，表明存在介导SRNA调控的其他新型机制。使用生物信息学方法，我们确定了在P.Gangivalis中，此处指定为PGR的RNA结合蛋白的候选者。我们的初步数据表明，蛋白质结合RNA并在硝化应激的细菌存活中起作用，因为 以及宿主细胞的存在。此外，我们注意到由于PGR缺失而导致的RNA水平发生了显着变化。基于初步数据，我们假设PGR是一种新型的RNA伴侣，并且在牙龈假单胞菌的转录后调节中起主要作用。由于PGR功能与细菌的完全毒力相关，因此它将成为发展抗菌策略的绝佳目标。为了深入了解蛋白质调节机制，我们将定义受蛋白质不存在影响的转录组和蛋白质组，并确定与PGR相互作用的RNA。我们预计，一旦完成这项工作，这项工作将提供有关该蛋白质作用机理的洞察力，并最终将导致设计策略干扰其作用，从而降低牙龈疟原虫的毒力。最后，我们预测这项工作将阐明其他相关细菌（例如Prevotella Intermedia，Tannerella forsythensis，cabteroides fragilis，B。thetaiotaomicomicron和Capnocytopnocytopnocytophaga hutchinsonii）中核糖调节的机制。