Quorum sensing (QS) is a cell-cell communication mechanism that enables bacteria to assess their population density and alter their behavior upon reaching high cell number. Many bacterial pathogens utilize QS to initiate an attack on their host, thus QS has attracted significant attention as a potential antivirulence alternative to traditional antibiotics. Streptococcus pneumoniae, a notorious human pathogen responsible for a variety of acute and chronic infections, utilizes the competence regulon and its associated signaling peptide, the competence stimulating peptide (CSP), to acquire antibiotic resistance and establish an infection. In this work, we sought to define the binding pockets within the ComD1 receptor used for binding the hydrophobic side-chain residues in CSP1 through the introduction of highly-conservative point mutations within the peptide. Optimization of these binding interactions could lead to the development of highly potent CSP-based QS modulators while the inclusion of non-natural amino acids within the CSP sequence would confer resistance to protease degradation, a requirement for drug candidates.

中文翻译：

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定义在肺炎链球菌中驱动能力刺激肽（CSP）-ComD结合的疏水相互作用。

群体感应（QS）是一种细胞间通信机制，可使细菌评估其种群密度并在达到高细胞数时改变其行为。许多细菌性病原体利用QS对其宿主发起攻击，因此QS作为传统抗生素的潜在抗毒替代品已引起广泛关注。肺炎链球菌是引起各种急性和慢性感染的臭名昭著的人类病原体，它利用能力调节剂及其相关的信号肽，即能力刺激肽（CSP）获得抗生素耐药性并建立感染。在这项工作中 我们试图通过在肽中引入高度保守的点突变来定义ComD1受体内的结合袋，该结合袋用于结合CSP1中的疏水侧链残基。这些结合相互作用的最优化可以导致开发高效的基于CSP的QS调节剂，而CSP序列中包含非天然氨基酸将赋予对蛋白酶降解的抗性，这是候选药物的要求。