Quorum-sensing synthase mutations re-calibrate autoinducer concentrations in clinical isolates of Pseudomonas aeruginosa to enhance pathogenesis.
Quorum-sensing synthase mutations re-calibrate autoinducer concentrations in clinical isolates of Pseudomonas aeruginosa to enhance pathogenesis.
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群体感应合酶突变重新校准铜绿假单胞菌临床分离株中的自诱导剂浓度，以增强发病机制。
DOI：
10.1038/s41467-023-43702-4
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发表时间：
2023-12-02
影响因子：
16.6
通讯作者：
Paczkowski, Jon E.
中科院分区：
文献类型：
--
作者：
Simanek, Kayla A.;Schumacher, Megan L.;Mallery, Caleb P.;Shen, Stella;Li, Lingyun;Paczkowski, Jon E.
群体感应是一种控制毒力基因表达的细菌交流机制。铜绿假单胞菌通过LasI/R和RhlI/R两对合成酶/转录因子受体调控毒力。LasR被认为是群体感应的主要转录调节因子，因为它上调了rhlI/R。然而，临床分离株通常在lasR中具有灭活突变，同时维持rhl依赖性信号。我们试图了解具有lasR突变的分离株的群体感应如何进展，特别是通过激活RhlR。我们发现具有lasR失活突变的临床分离株通常在rhlI中同时存在突变。利用超高效液相色谱和高分辨率质谱分析，我们发现缺乏激光r的菌株过量生产了RhlI合成的自诱导剂，并且RhlI变体将自诱导剂浓度重新校准到野生型水平，恢复了毒力表型。这些发现为急性感染生态位中群体感应进程的可塑性提供了一种机制。Simanek等人发现，在负责合成细菌交流所需分子的蛋白质中出现了变异，这种分子介导了铜绿假单胞菌的毒力进展。
Quorum sensing is a mechanism of bacterial communication that controls virulence gene expression. Pseudomonas aeruginosa regulates virulence via two synthase/transcription factor receptor pairs: LasI/R and RhlI/R. LasR is considered the master transcriptional regulator of quorum sensing, as it upregulates rhlI/R. However, clinical isolates often have inactivating mutations in lasR, while maintaining Rhl-dependent signaling. We sought to understand how quorum sensing progresses in isolates with lasR mutations, specifically via activation of RhlR. We find that clinical isolates with lasR inactivating mutations often harbor concurrent mutations in rhlI. Using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we discover that strains lacking lasR overproduce the RhlI-synthesized autoinducer and that RhlI variants re-calibrate autoinducer concentrations to wild-type levels, restoring virulent phenotypes. These findings provide a mechanism for the plasticity of quorum sensing progression in an acute infection niche. Simanek et al. discovered variants that arise in the protein responsible for synthesizing a molecule required for bacterial communication, which mediates the progression of virulence in the pathogen Pseudomonas aeruginosa.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
14.9
作者：
Letunic I;Bork P
通讯作者：
Bork P
影响因子：
3.1
作者：
Harrison F;Muruli A;Higgins S;Diggle SP
通讯作者：
Diggle SP
影响因子：
3.6
作者：
Diggle, SP;Winzer, K;Williams, P
通讯作者：
Williams, P
DOI：
10.1073/pnas.1819801116
发表时间：
2019-04-02
影响因子：
11.1
作者：
Chen, Ruiyi;Deziel, Eric;Greenberg, E. Peter
通讯作者：
Greenberg, E. Peter