Mechanisms of RsaL mediated tolerance to ciprofloxacin and carbenicillin in Pseudomonas aeruginosa
Mechanisms of RsaL mediated tolerance to ciprofloxacin and carbenicillin in Pseudomonas aeruginosa
复制标题
RsaL介导铜绿假单胞菌对环丙沙星和羧苄青霉素耐受的机制
DOI：
10.1007/s00294-018-0863-3
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发表时间：
2019-02-01
期刊：
影响因子：
2.5
通讯作者：
Wu, Weihui
中科院分区：
文献类型：
--
作者：
Fan, Zheng;Xu, Chang;Wu, Weihui
铜绿假单胞菌RsaL是群体感应信号合成基因lasI的负调节因子。RsaL的表达由LasI同源调节子LasR直接激活。因此，RsaL和LasI-LasR（LasI/R）形成调节环。进一步的研究表明RsaL是一个全局性的调节因子，通过群体感应系统依赖和非依赖的途径调控许多基因的表达。然而，RsaL是否参与抗生素耐受性仍然难以捉摸。在本研究中，我们发现rsaL突变增加了细菌对环丙沙星和羧苄青霉素的耐受性。通过模体搜索、基因表达分析和电泳迁移率变动分析，我们发现RsaL直接抑制narK 1 K2 GHJI操纵子的表达，该操纵子参与对环丙沙星的耐受。我们进一步证明了narK 1 K2 GHJI操纵子直接受LasR调控。结合，我们的研究揭示了一种新的操纵子的控制下的RsaL，LasI/R调节环。
The Pseudomonas aeruginosa RsaL is a negative regulator of the quorum sensing signal synthesis gene lasI. The expression of RsaL is directly activated by the LasI cognate regulator LasR. Thus, RsaL and LasI-LasR (LasI/R) form a regulatory loop. Further studies revealed that RsaL is a global regulator which controls the expression of numerous genes through quorum sensing system dependent and independent pathways. However, whether RsaL is involved in antibiotic tolerance remains elusive. In this study, we found that the mutation of rsaL increased bacterial tolerance to ciprofloxacin and carbenicillin. Through motif search, gene expression analyses and electrophoretic mobility shift assays, we found that RsaL directly represses the expression of the narK1K2GHJI operon, which is involved in the tolerance to ciprofloxacin. We further demonstrated that the narK1K2GHJI operon is directly regulated by LasR. In combination, our study revealed a novel operon under the control of the RsaL, LasI/R regulatory loop.