Elucidating the Interplay between the ComRS and the ComABCDE Quorum Sensing Circuitries in Streptococci

在化学系生命过程化学项目的支持下，来自内华达大学雷诺分校的Tal-Gan教授正在研究同一物种细菌内的多条通讯途径如何影响细菌的行为。细菌利用一种化学信号的语言相互交流，评估他们的环境，并在种群水平上协调行为变化。一些细菌物种产生多种化学信号，每个信号对应不同的信息，并导致不同的行为反应。然而，在某些情况下，两个不同的信号可以通过不同的交流途径导致类似的行为反应。这项拟议的研究旨在从分子水平上描述同一种细菌中不同的通讯途径如何相互影响，从而间接影响另一种通讯途径调控的行为。了解不同通信途径之间的相互作用和层次结构可以为管理和控制不同环境中的细菌行为铺平道路。这项研究将允许本科生和研究生获得化学和微生物学方面的专业培训，从合成多肽化学和分析表征到微生物学和分子生物学技术。该项目还将被整合到一个推广计划中，旨在为宾夕法尼亚州伊斯顿的拉斐特学院的本科生和教职员工提供化学和生物学界面的动手研究经验。该项目旨在利用变形链球菌作为模型系统，在分子水平上研究类ComABCDE和ComRS群体感应电路之间的相互作用和层次结构。链球菌遗传转化的能力受能力调节蛋白的调控，依赖于一种称为群体感应的细胞-细胞信号机制。在一些链球菌中，能力调节子由一个两组分的QS回路组成，称为ComABCDE回路，而在另一些物种中，能力调节子由一个RRNPP类型的QS回路组成，称为ComRS回路。重要的是，一些种类的链球菌同时具有ComABCDE样回路和ComRS样回路。拟议的跨学科项目将把化学生物学技术与传统的微生物学方法相结合，以实现以下目标：1)描绘控制变形链球菌中ComABCDE样和ComRS QS电路之间相互作用的分子机制；以及2)将ComABCDE样电路和ComRS QS电路之间的相互作用规则扩展和推广到其他细菌物种。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Professor Tal-Gan from the University of Nevada, Reno is studying how multiple communication pathways within the same species of bacteria affect bacterial behavior. Bacteria utilize a language of chemical signals to communicate with each other, assess their environment, and coordinate behavioral changes at the population level. Some bacterial species produce multiple chemical signals, each of which correspond to a different message and result in different behavioral responses. However, in some cases, two different signals can lead to a similar behavioral response through alternative communication pathways. The proposed study aims to characterize, at the molecular level, how different communication pathways within the same species of bacteria affect one another and consequently indirectly affect behaviors regulated by the other communication pathway. Understanding the interplay and hierarchy between different communication pathways could pave the way to manage and control bacterial behavior in diverse environmental niches. This study will allow undergraduate and graduate students to acquire specialized training in both chemistry and microbiology, from synthetic peptide chemistry and analytical characterization to microbiology and molecular biology techniques. This project also will be integrated into an outreach program aimed at providing undergraduate students and faculty from Lafayette College, a small liberal arts college in Easton, Pennsylvania, experience in hands-on research at the interface of chemistry and biology.This project aims to utilize Streptococcus mutans as a model system to study the interplay and hierarchy between the ComABCDE-like and ComRS quorum sensing circuitries at the molecular level. Competence for genetic transformation in streptococci is regulated by the competence regulon and relies on a cell-cell signaling mechanism, termed quorum sensing (QS). In some streptococci species the competence regulon is composed of a two-component-based QS circuit, termed the ComABCDE circuitry, while in other species, the competence regulon is composed of an RRNPP-type QS circuit, termed the ComRS circuitry. Importantly, some species of streptococci possess both a ComABCDE-like circuit and a ComRS-like circuitry. The proposed interdisciplinary project will integrate chemical biology techniques with traditional microbiology approaches to pursue the following objectives: 1) delineate the molecular mechanisms that govern the interplay between the ComABCDE-like and ComRS QS circuits in S. mutans; and 2) expand and generalize the rules governing the interplay between the ComABCDE-like and ComRS QS circuits to other bacterial species.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.