<br>基于细菌生物传感器的群体感应抑制剂的高通量、定量筛选,ACS Chemical Biology

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基于细菌生物传感器的群体感应抑制剂的高通量、定量筛选
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2023-11-20 , DOI: 10.1021/acschembio.3c00537
Jun-Wei Zhang ₁ , Cong Guo ₁ , Chen-Guang Xuan ₁ , Jing-Wen Gu ₂ , Zi-Ning Cui _{2,

3} , Jing Zhang ₄ , Lixin Zhang ₄ , Wenjun Jiang ₁ , Li-Qun Zhang ₁

Affiliation

群体感应（QS）是一种细胞间通讯机制，细菌通过产生和感知小分子信号来同步社会行为，例如生物膜形成和毒力因子分泌。通过降解信号或阻断信号传输的群体猝灭（QQ）已成为破坏 QS 并防止细菌感染和生物膜形成的有前途的策略。然而，群体感应抑制剂（QSI）的高通量筛选和鉴定方法的研究仍然不足。在这项工作中，我们开发了一种基于细菌生物传感器菌株根癌农杆菌N5 (pBA7P) 的灵敏、高通量的 QSI 筛选方法，该菌株含有由 QS 信号诱导的traG基因启动子，该启动子与无启动子的 β-内酰胺酶基因报告基因融合。利用这种方法，我们从约 2000 个土壤细菌分离株中鉴定出了 31 种 QQ 细菌，其中一些属于Bosea属、 Cupriavidus 属和黄杆菌属，之前未曾报道为 QQ 细菌。我们还从约 5000 种小分子化合物中鉴定出了四种 QS 抑制化合物和一种 QS 信号类似物，它们深刻影响了病原菌 QS 调节基因的表达和表型。这种高通量筛选系统可有效且灵敏地筛选 QQ 微生物和小分子，从而能够发现多种生物相容性化合物。

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High-Throughput, Quantitative Screening of Quorum-Sensing Inhibitors Based on a Bacterial Biosensor

Quorum sensing (QS) is a cell–cell communication mechanism by which bacteria synchronize social behaviors such as biofilm formation and virulence factor secretion by producing and sensing small molecular signals. Quorum quenching (QQ) by degrading signals or blocking signal transmissions has become a promising strategy for disrupting QS and preventing bacterial infection and biofilm formation. However, studies of high-throughput screening and identification approaches for quorum-sensing inhibitors (QSIs) are still inadequate. In this work, we developed a sensitive, high-throughput approach for screening QSIs based on the bacterial biosensor strain Agrobacterium tumefaciens N5 (pBA7P), which contains a traG gene promoter induced by QS signals fused with a promoterless β-lactamase gene reporter. Using this approach, we identified 31 QQ bacteria from ∼2000 soil bacterial isolates, some belonging to the genera Bosea, Cupriavidus, and Flavobacterium that have not been reported previously as QQ bacteria. We also identified four QS inhibitory compounds and one QS signal analogue from ∼5000 small-molecule compounds, which profoundly affected the expression of QS-regulated genes and phenotypes of the pathogenic bacteria. This high-throughput screening system is effective and sensitive for screening of both QQ microbes and small molecules, enabling the discovery of a wide variety of biocompatible compounds.

更新日期：2023-11-20

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