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A Pro-Drug Approach for Selective Modulation of AI-2-Mediated Bacterial Cell-to-Cell Communication

机译:一种AI-2介导的细菌细胞间通信选择性调制的前药方法。

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摘要

The universal quorum sensing autoinducer, AI-2, is utilized by several bacteria. Analogs of AI-2 have the potential to modulate bacterial behavior. Selectively quenching the communication of a few bacteria, in the presence of several others in an ecosystem, using analogs of AI-2 is non-trivial due to the ubiquity of AI-2 processing receptors in many bacteria that co-exist. Herein, we demonstrate that when an AI-2 analog, isobutyl DPD (which has been previously shown to be a quorum sensing, QS, quencher in both Escherichia coli and Salmonella typhimurium) is modified with ester groups, which get hydrolyzed once inside the bacterial cells, only QS in E. coli, but not in S. typhimurium, is inhibited. The origin of this differential QS inhibition could be due to differences in analog permeation of the bacterial membranes or ester hydrolysis rates. Such differences could be utilized to selectively target QS in specific bacteria amongst a consortium of other species that also use AI-2 signaling.
机译:通用群体感应自动感应器AI-2被几种细菌利用。 AI-2的类似物具有调节细菌行为的潜力。使用AI-2的类似物,在生态系统中存在其他几种细菌的情况下,有选择地淬灭几种细菌的通讯是很重要的,因为在许多共存的细菌中,AI-2处理受体普遍存在。在本文中,我们证明,当AI-2类似物异丁基DPD(先前已证明是群体感应,QS,在大肠杆菌和鼠伤寒沙门氏菌中的淬灭剂)被酯基修饰时,该酯基一旦在细菌内部被水解即可。在大肠杆菌中,只有QS被抑制,而鼠伤寒沙门氏菌则没有。这种不同的QS抑制作用的起因可能是由于细菌膜的类似物渗透率或酯水解速率不同。这样的差异可用于在也使用AI-2信号转导的其他物种财团中选择性靶向特定细菌中的QS。

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