The antitoxin MqsA homologue in Pseudomonas fluorescens 2P24 has a rewired regulatory circuit through evolution
The antitoxin MqsA homologue in Pseudomonas fluorescens 2P24 has a rewired regulatory circuit through evolution
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荧光假单胞菌 2P24 中的抗毒素 MqsA 同源物通过进化重新构建了调控电路
DOI：
10.1111/1462-2920.14538
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发表时间：
2019-05-01
影响因子：
5.1
通讯作者：
He, Yong-Xing
中科院分区：
文献类型：
--
作者：
Wang, Yong;Zhang, Si-Ping;He, Yong-Xing
mqsRA操纵子编码一个毒素-抗毒素对，其特征是参与大肠杆菌的生物膜和持久性细胞的形成。值得注意的是，抗毒素MqsA具有c端dna结合域，可识别[5'-AACCT(N)2-4 AGGTT-3']基序，并作为转录调节剂控制包括一般应激反应调节剂RpoS在内的多个基因。然而，目前尚不清楚MqsA同源物在细菌中的转录回路在进化过程中是如何变化的。本文中，我们发现荧光假单胞菌中的mqsA （PfmqsA）是通过水平基因转移获得的，并结合在PfmqsRA操纵子上游的一个略有不同的基序[5'-TACCCT(N)3 AGGGTA-3']上。有趣的是，一个相邻的gntr型转录调节因子，被称为AgtR，在PfMqsA的阴性控制下。进一步证明PfMqsA通过AgtR减少生物膜组分的产生，而AgtR直接调控参与胞外聚合物质合成的pga和fap操纵子。此外，通过定量蛋白质组学分析，我们发现AgtR是一个高度多效性的调节剂，影响多达252个基因，这些基因与化学趋向性、氧化磷酸化和碳氮代谢等多种过程相关。综上所述，我们的研究结果表明，PfMqsA的重新连接的调节回路通过新表征的AgtR影响荧光P. 2P24的多种生理方面。
The mqsRA operon encodes a toxin-antitoxin pair that was characterized to participate in biofilm and persister cell formation in Escherichia coli. Notably, the antitoxin MqsA possesses a C-terminal DNA-binding domain that recognizes the [5'-AACCT(N)2-4 AGGTT-3'] motif and acts as a transcriptional regulator controlling multiple genes including the general stress response regulator RpoS. However, it is unknown how the transcriptional circuits of MqsA homologues have changed in bacteria over evolutionary time. Here, we found mqsA in Pseudomonas fluorescens (PfmqsA) is acquired through horizontal gene transfer and binds to a slightly different motif [5'-TACCCT(N)3 AGGGTA-3'], which exists upstream of the PfmqsRA operon. Interestingly, an adjacent GntR-type transcriptional regulator, which was termed AgtR, is under negative control of PfMqsA. It was further demonstrated that PfMqsA reduces production of biofilm components through AgtR, which directly regulates the pga and fap operons involved in the synthesis of extracellular polymeric substances. Moreover, through quantitative proteomics analysis, we showed AgtR is a highly pleiotropic regulator that influences up to 252 genes related to diverse processes including chemotaxis, oxidative phosphorylation and carbon and nitrogen metabolism. Taken together, our findings suggest the rewired regulatory circuit of PfMqsA influences diverse physiological aspects of P. fluorescens 2P24 via the newly characterized AgtR.