Mehrani Mona, Mull Ryan W, Guo Mingzhe, Renshaw Clay P, Singh Robbin J, Tal-Gan Yftah
Department of Chemistry, University of Nevada, Reno, 1664 North Virginia Street, Reno, Nevada 89557, United States.
Biochemistry. 2025 Jul 15;64(14):3104-3113. doi: 10.1021/acs.biochem.5c00195. Epub 2025 Jun 23.
, a member of the group (SAG), is a Gram-positive bacterial species commonly found in the oral and gastrointestinal tracts; however, it can become pathogenic, particularly in immunocompromised individuals. is associated with the development of purulent infections that typically require a combination of antibiotic therapy and surgical intervention for effective treatment. This understudied emerging pathogen appears to possess a quorum sensing (QS) circuitry, which is common in many streptococci species; however, the molecular interactions that drive this circuitry and its regulatory function remain unexplored. Herein, we confirmed the identity of the competence-stimulating peptide (CSP) and performed phenotypic assays to investigate its regulatory role in competence and biofilm development. To examine the role of each amino acid within the CSP sequence in QS activity, we conducted d-amino acid and alanine scans of the CSP. Given the uniquely high natural QS induction observed in , we developed a Δ luciferase reporter system to assess the activity of the d-amino acid and alanine scan analogs on the competence regulon. Our results revealed that a single Alanine substitution could lead to a 60-fold increase in CSP potency. Furthermore, through circular dichroism (CD) analysis, we investigated the correlation between the secondary structure and biological activity. Overall, this study aims to enhance our understanding of , a relatively understudied species with pathogenic potential, and aid in the development of strategies to mitigate its pathogenicity.
作为 组（SAG）的一员，是一种革兰氏阳性细菌，常见于口腔和胃肠道；然而，它可能会致病，尤其是在免疫功能低下的个体中。 与化脓性感染的发生有关，通常需要联合抗生素治疗和手术干预才能有效治疗。这种研究较少的新兴病原体似乎拥有一种群体感应（QS）电路，这在许多链球菌物种中很常见；然而，驱动这种电路的分子相互作用及其调节功能仍未被探索。在此，我们确认了 感受态刺激肽（CSP）的身份，并进行了表型分析以研究其在感受态和生物膜形成中的调节作用。为了研究CSP序列中每个氨基酸在QS活性中的作用，我们对 CSP进行了d - 氨基酸和丙氨酸扫描。鉴于在 中观察到的独特的高天然QS诱导，我们开发了一种Δ荧光素酶报告系统来评估d - 氨基酸和丙氨酸扫描类似物对感受态调节子的活性。我们的结果表明，单个丙氨酸取代可导致CSP效力增加60倍。此外，通过圆二色性（CD）分析，我们研究了二级结构与生物活性之间的相关性。总体而言，本研究旨在加深我们对 这种具有致病潜力但研究相对较少的物种的理解，并有助于制定减轻其致病性的策略。
