Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR in Pseudomonas aeruginosa.,Molecular Microbiology

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Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR in Pseudomonas aeruginosa.
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-08-04 , DOI: 10.1111/mmi.14584
Tietao Wang ₁ , Yihang Qi ₁ , Zhihan Wang ₂ , Jingru Zhao ₁ , Linxuan Ji ₁ , Jun Li ₃ , Zhao Cai ₄ , Liang Yang ₄ , Min Wu ₅ , Haihua Liang ₁

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The GntR family regulators are widely distributed in bacteria and play critical roles in metabolic processes and bacterial pathogenicity. In this study, we describe a GntR family protein encoded by PA4132 that we named MpaR (MvfR‐mediated PQS and anthranilate regulator) for its regulation of Pseudomonas quinolone signal (PQS) production and anthranilate metabolism in Pseudomonas aeruginosa. The deletion of mpaR increased biofilm formation and reduced pyocyanin production. RNA sequencing analysis revealed that the mRNA levels of antABC encoding enzymes for the synthesis of catechol from anthranilate, a precursor of the PQS, were most affected by mpaR deletion. Data showed that MpaR directly activates the expression of mvfR, a master regulator of pqs system, and subsequently promotes PQS production. Accordingly, deletion of mpaR activates the expression of antABC genes, and thus, increases catechol production. We also demonstrated that MpaR represses the rhl quorum‐sensing (QS) system, which has been shown to control antABC activity. These results suggested that MpaR function is integrated into the QS regulatory network. Moreover, mutation of mpaR promotes bacterial survival in a mouse model of acute pneumonia infection. Collectively, this study identified a novel regulator of pqs system, which coordinately controls anthranilate metabolism and bacterial virulence in P. aeruginosa.

中文翻译：

铜绿假单胞菌中 GntR 家族调节剂 MpaR 对邻氨基苯甲酸代谢和细菌毒力的协调调节。

GntR 家族调节因子广泛分布于细菌中，在代谢过程和细菌致病性中起关键作用。在这项研究中，我们描述PA4132编码，我们命名为MPAR（一GntR家族蛋白中号VFR介导的P QS和一个nthranilate [R egulator）对其的调控假单胞菌喹诺酮类信号（PQS）的生产和苯甲酸代谢的绿脓杆菌。mpaR的缺失增加了生物膜的形成并减少了绿脓素的产生。RNA测序分析显示antABC的mRNA水平从邻氨基苯甲酸（PQS 的前体）合成儿茶酚的编码酶受mpaR缺失的影响最大。数据显示，MpaR 直接激活pqs系统的主要调节因子mvfR的表达，进而促进 PQS 的产生。因此，mpaR 的缺失会激活antABC基因的表达，从而增加儿茶酚的产生。我们还证明了 MpaR 抑制了rhl群体感应 (QS) 系统，该系统已被证明可以控制antABC 的活性。这些结果表明 MpaR 功能已集成到 QS 监管网络中。此外，mpaR 的突变在急性肺炎感染小鼠模型中促进细菌存活。总的来说，这项研究确定了pqs系统的新调节剂，它协调控制P 中的邻氨基苯甲酸代谢和细菌毒力。铜绿假单胞菌。

更新日期：2020-08-04

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