Elucidating Rgg-mediated quorum sensing networks in Streptococcus pneumoniae and their contributions in pathogenesis

摘要 群体感应（QS），或通过细胞间化学信号传导的细菌通信，是许多细菌（如果 不是大多数）细菌物种;然而，尚不清楚QS信号通路如何在许多临床上导致毒力。 重要病原体。Federle实验室帮助描述了一个转录调节因子家族，称为Rgg 蛋白质，作为QS的介质。我们和其他人已经证明了Rgg蛋白在多个物种中的重要性。 链球菌在调节基因表达中的作用，这些基因可能增强其定殖和感染宿主的能力。RGG蛋白质类 已知调节基因对于1）控制毒力; 2）促进抗性的发展， 溶菌酶，宿主产生的抗微生物酶; 3）刺激生物膜或保护性细菌的形成 4）启动从环境中摄取DNA的自然能力的发展;以及5） 促进粘附于上皮细胞的能力。Rgg蛋白在临床疾病患者致病生活方式中的作用 重要病原菌S.肺炎还有待研究，但已发表的基因组水平诱变研究表明， 这种生物体中的Rgg蛋白在体内感染动物模型中至关重要。我们已经构建了同基因突变体， 每种Rgg蛋白在体内都很重要，并且已经进行了转录组学分析以鉴定Rgg下的基因靶标。 调控我们的分析揭示了肺炎球菌中Rgg蛋白SP_0141调控的18个基因靶点， 包囊菌株TIGR 4（血清型4）。我们正在测试感兴趣的基因靶点， rgg介导的QS及其在毒力中的作用。然后，我们将探讨使用QS来调节 在免疫监视的存在下的发病机制。了解QS调控下的分子网络和 在宿主中使用QS的优势将为调节QS作为有效策略的可能性提供支持， 对抗病原体

Abstract Quorum Sensing (QS), or bacterial communication by intercellular chemical signaling, is a process common to many (if not most) bacterial species; yet, it is unclear how QS signaling pathways contribute to virulence in many clinically significant pathogens. The Federle lab has helped to characterize a family of transcriptional regulators, known as Rgg proteins, as mediators of QS. We and others have shown the importance of Rgg proteins in multiple species of streptococci in regulating expression of genes that may enhance their ability to colonize and infect the host. Rgg proteins are known to regulate genes important for 1) controlling virulence; 2) promoting the development of resistance to lysozyme, a host-produced antimicrobial enzyme; 3) stimulating the formation of biofilms, or protective bacterial communities; 4) initiating the development of natural competence to take up DNA from the environment; and 5) promoting the ability to adhere to epithelial cells. The role of the Rgg proteins in the pathogenic lifestyle of the clinically significant pathogen S. pneumoniae has yet to be investigated, but published genome-level mutagenesis studies indicate Rgg proteins in this organism are critical in in vivo animal models of infection. We have constructed isogenic mutants for each Rgg protein important in vivo and have performed transcriptomic analysis to identify gene targets under Rgg- regulation. Our analysis has revealed 18 gene targets under regulation by the Rgg protein SP_0141 in the pneumococcal encapsulated strain TIGR4 (serotype 4). We are in the process of testing gene targets of interest in order to understand Rgg-mediated QS and its role in virulence. We will then explore the consequences of using QS to regulate mechanisms of pathogenesis in the presence of immune surveillance. Understanding the molecular networks under QS regulation and the advantage of using QS in the host will provide support for the possibility of modulating QS as an effective strategy for combatting pathogens.