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Quorum Sensing Signals Form Complexes with Ag+ and Cu2+ Cations
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2018-03-06 00:00:00 , DOI: 10.1021/acschembio.7b01000
Eric McGivney 1, 2 , Kayleigh Elizabeth Jones 3 , Bandrea Weber 1 , Ann Margaret Valentine 3 , Jeanne M. VanBriesen 1, 2 , Kelvin B. Gregory 1, 2
Affiliation  

Quorum sensing (QS) regulates important bacterial behaviors such as virulent protein production and biofilm formation. QS requires that molecular signals are exchanged between cells, extracellularly, where environmental conditions influence signal stability. In this work, we present a novel complexation between metal cations (Ag+ and Cu2+) and a QS autoinducer signal, N-hexanoyl-L-homoserine lactone (HHL). The molecular interactions were investigated using mass spectrometery, attenuated total reflectance—Fourier transform infrared spectroscopy, and computational simulations. Results show that HHL forms predominantly 1:1 complexes with Ag+ (Kd = 3.41 × 10–4 M) or Cu2+ (Kd = 1.40 × 10–5 M), with the coordination chemistry occurring on the oxygen moieties. In vivo experiments with Chromobacterium violaceum CV026 show that sublethal concentrations of Ag+ and Cu2+ decreased HHL-regulated QS activity. Furthermore, when Ag+ was preincubated with HHL, Ag+ toxicity to CV026 decreased by an order of magnitude, suggesting HHL:metal complexes alter the bioavailability of the individual constituents.

中文翻译:

群体感应信号与Ag +和Cu 2+阳离子形成络合物

群体感应(QS)调节重要的细菌行为,例如有毒的蛋白质生产和生物膜形成。QS要求在环境条件影响信号稳定性的细胞外细胞间交换分子信号。在这项工作中,我们提出了金属阳离子(Ag +和Cu 2+)与QS自诱导信号N-己基-L-高丝氨酸内酯(HHL)之间的新型络合物。使用质谱仪,衰减的全反射-傅立叶变换红外光谱法和计算模拟研究了分子相互作用。结果表明,HHL与Ag +K d = 3.41×10 –4)主要形成1:1的络合物。M)或Cu 2+K d = 1.40×10 –5 M),配位化学反应发生在氧部分上。紫色杆菌CV026的体内实验表明,亚致死浓度的Ag +和Cu 2+降低了HHL调节的QS活性。此外,当将Ag +与HHL预孵育时,Ag +对CV026的毒性降低了一个数量级,表明HHL:金属络合物改变了各个成分的生物利用度。
更新日期:2018-03-06
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