Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover
Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover
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DOI：
10.1073/pnas.1205037109
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发表时间：
2012-09-18
影响因子：
11.1
通讯作者：
Zhang, Lian-Hui
中科院分区：
文献类型：
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作者：
Deng, Yinyue;Schmid, Nadine;Zhang, Lian-Hui
许多细菌病原体产生可扩散信号因子（DSF）型群体感应（QS）信号，调节毒力和生物膜形成。以前的研究表明，黄单胞菌的RpfC/RpfG双组分系统参与DSF信号的感知和响应，但在其他微生物中知之甚少。在这里，我们表明，在伯克霍尔德氏菌cenocepacia的DSF家族信号顺式-2-十二碳烯酸（BDSF）负控制细胞内的环二聚鸟苷酸（c-di-GMP）水平通过受体蛋白RpfR，其中包含Per/Arnt/Sim（PAS）-GGDEF-EAL结构域。RpfR调节与BDSF相同的表型，包括群集运动性、生物膜形成和毒力。此外，可以通过RpfR或其EAL结构域（充当c-di-GMP磷酸二酯酶）的反式表达来拯救BDSF突变表型。BDSF显示以高亲和力结合RpfR的PAS结构域，并通过诱导变构构象变化刺激其磷酸二酯酶活性。我们的工作提出了一个独特的和广泛保守的DSF家族信号受体，直接连接的信号感知c-di-GMP营业额在细菌生理调节。
Many bacterial pathogens produce diffusible signal factor (DSF)-type quorum sensing (QS) signals in modulation of virulence and biofilm formation. Previous work on Xanthomonas campestris showed that the RpfC/RpfG two-component system is involved in sensing and responding to DSF signals, but little is known in other microorganisms. Here we show that in Burkholderia cenocepacia the DSF-family signal cis-2-dodecenoic acid (BDSF) negatively controls the intracellular cyclic dimeric guanosine monophosphate (c-di-GMP) level through a receptor protein RpfR, which contains Per/Arnt/Sim (PAS)-GGDEF-EAL domains. RpfR regulates the same phenotypes as BDSF including swarming motility, biofilm formation, and virulence. In addition, the BDSF-mutant phenotypes could be rescued by in trans expression of RpfR, or its EAL domain that functions as a c-di-GMP phosphodiesterase. BDSF is shown to bind to the PAS domain of RpfR with high affinity and stimulates its phosphodiesterase activity through induction of allosteric conformational changes. Our work presents a unique and widely conserved DSF-family signal receptor that directly links the signal perception to c-di-GMP turnover in regulation of bacterial physiology.