Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR inPseudomonas aeruginosa
Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR inPseudomonas aeruginosa
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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
DOI：
10.1111/mmi.14584
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发表时间：
2020
影响因子：
3.6
通讯作者：
Liang Haihua
中科院分区：
文献类型：
--
作者：
Wang Tietao;Qi Yihang;Wang Zhihan;Zhao Jingru;Ji Linxuan;Li Jun;Cai Zhao;Yang Liang;Wu Min;Liang Haihua
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发挥着关键作用。在这项研究中，我们描述了由 PA4132 编码的 GntR 家族蛋白，我们将其命名为 MpaR（MvfR 介导的 PQS 和邻氨基苯甲酸调节剂），因为它调节铜绿假单胞菌中的假单胞菌喹诺酮信号 (PQS) 产生和邻氨基苯甲酸代谢。 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，用于从邻氨基苯甲酸（PQS的前体）合成儿茶酚的antABC编码酶的mRNA水平受mpaR缺失的影响最大。数据显示，MpaR直接激活pqs系统主调节因子mvfR的表达，随后促进PQS的产生。因此，mpaR的缺失激活antABC基因的表达，并因此增加儿茶酚的产生。我们还证明了 MpaR 抑制群体感应 (QS) 系统，该系统已被证明可以控制 ABC 活性。这些结果表明 MpaR 功能已整合到 QS 调节网络中。此外，mpaR 的突变可促进急性肺炎感染小鼠模型中的细菌存活。总的来说，这项研究确定了 pqs 系统的一种新型调节剂，它协调控制铜绿假单胞菌中的邻氨基苯甲酸盐代谢和细菌毒力。
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‐mediatedPQS andanthranilateregulator) for its regulation ofPseudomonasquinolone signal (PQS) production and anthranilate metabolism inPseudomonas aeruginosa. The deletion ofmpaRincreased biofilm formation and reduced pyocyanin production. RNA sequencing analysis revealed that the mRNA levels ofantABCencoding enzymes for the synthesis of catechol from anthranilate, a precursor of the PQS, were most affected bympaRdeletion. Data showed that MpaR directly activates the expression ofmvfR, a master regulator ofpqssystem, and subsequently promotes PQS production. Accordingly, deletion ofmpaRactivates the expression ofantABCgenes, and thus, increases catechol production. We also demonstrated that MpaR represses therhlquorum‐sensing (QS) system, which has been shown to controlantABCactivity. These results suggested that MpaR function is integrated into the QS regulatory network. Moreover, mutation ofmpaRpromotes bacterial survival in a mouse model of acute pneumonia infection. Collectively, this study identified a novel regulator ofpqssystem, which coordinately controls anthranilate metabolism and bacterial virulence inP.aeruginosa.