Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.
Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, China.
Environ Microbiol. 2020 Oct;22(10):4424-4437. doi: 10.1111/1462-2920.15144. Epub 2020 Jul 28.
In our previous study, we found that pumilacidin-like cyclic lipopeptides (CLPs) derived from marine bacterium Bacillus sp. strain 176 significantly suppressed the mobile capability and virulence of Vibrio alginolyticus. Here, to further disclose the mechanism of CLPs inhibiting the motility of V. alginolyticus, we first applied transcriptomic analysis to V. alginolyticus treated with or without CLPs. The transcriptomic results showed that the expression of several important components of the Na -driven flagellar motor closely related to bacterial motility were markedly suppressed, suggesting that the structure and function of Na -driven flagellar motor might be disabled by CLPs. The transcriptomic data were further analysed by the protein-protein interaction network, and the results supported that MotX, one of the essential components of Na -driven flagellar motor was most likely the action target of CLPs. In combination of gene knockout, electrophoretic mobility shift assay and immunoblotting techniques, CLPs were demonstrated to affect the rotation of flagella of Vibrio alginolyticus via direct interacting with the Na -driven flagellar motor component MotX, which eventually inhibited the bacterial motility. Interestingly, homologues of MotX were found broadly distributed and highly conserved in different pathogenic species, which extends the application range of CLPs as an antibacterial drug targeting bacterial motility in many pathogens.
在我们之前的研究中，我们发现来源于海洋细菌芽孢杆菌 176 的短杆菌肽样环状脂肽 (CLP) 显著抑制了鳗弧菌的运动能力和毒力。在这里，为了进一步揭示 CLP 抑制鳗弧菌运动能力的机制，我们首先应用转录组分析来研究 CLP 处理或未处理的鳗弧菌。转录组结果表明，与细菌运动密切相关的 Na + 驱动鞭毛马达的几个重要组成部分的表达明显受到抑制，这表明 CLP 可能会破坏 Na + 驱动鞭毛马达的结构和功能。通过蛋白质-蛋白质相互作用网络对转录组数据进行了进一步分析，结果表明 MotX 是 Na + 驱动鞭毛马达的必需组成部分之一，极有可能是 CLP 的作用靶点。结合基因敲除、电泳迁移率变动分析和免疫印迹技术，证明 CLP 通过直接与 Na + 驱动鞭毛马达组件 MotX 相互作用，影响鳗弧菌鞭毛的旋转，从而最终抑制细菌的运动能力。有趣的是，MotX 的同源物广泛分布且在不同的致病性物种中高度保守，这将 CLP 作为一种针对许多病原体细菌运动能力的抗菌药物的应用范围扩大了。
