Wang Yaya, Cao Qiao, Cao Qin, Gan Jianhua, Sun Ning, Yang Cai-Guang, Bae Taeok, Wu Min, Lan Lefu
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; College of Life Science, Northwest University, Xi'an 710069, China.
Sci Bull (Beijing). 2021 Jun 15;66(11):1101-1118. doi: 10.1016/j.scib.2021.01.002. Epub 2021 Jan 5.
During infections, bacteria stimulate host cells to produce and release histamine, which is a key mediator of vital cellular processes in animals. However, the mechanisms underlying the bacterial cell's ability to sense and respond to histamine are poorly understood. Herein, we show that HinK, a LysR-type transcriptional regulator, is required to evoke responses to histamine in Pseudomonas aeruginosa, an important human pathogen. HinK directly binds to and activates the promoter of genes involved in histamine uptake and metabolism, iron acquisition, and Pseudomonas quinolone signal (PQS) biosynthesis. The transcriptional regulatory activity of HinK is induced when histamine is present, and it occurs when HinK binds with imidazole-4-acetic acid (ImAA), a histamine metabolite whose production in P. aeruginosa depends on the HinK-activated histamine uptake and utilization operon hinDAC-pa0222. Importantly, the inactivation of HinK inhibits diverse pathogenic phenotypes of P. aeruginosa. These results suggest that histamine acts as an interkingdom signal and provide insights into the mechanism used by pathogenic bacteria to exploit host regulatory signals to promote virulence.
在感染过程中，细菌刺激宿主细胞产生并释放组胺，组胺是动物重要细胞过程的关键介质。然而，细菌细胞感知和响应组胺的能力背后的机制仍知之甚少。在此，我们表明，HinK，一种LysR型转录调节因子，是铜绿假单胞菌（一种重要的人类病原体）对组胺产生反应所必需的。HinK直接结合并激活参与组胺摄取和代谢、铁获取以及铜绿假单胞菌喹诺酮信号（PQS）生物合成的基因的启动子。当存在组胺时，HinK的转录调节活性被诱导，并且当HinK与咪唑-4-乙酸（ImAA）结合时发生，ImAA是一种组胺代谢产物，其在铜绿假单胞菌中的产生取决于HinK激活的组胺摄取和利用操纵子hinDAC-pa0222。重要的是，HinK的失活抑制了铜绿假单胞菌的多种致病表型。这些结果表明组胺作为一种跨界信号，并为病原菌利用宿主调节信号促进毒力的机制提供了见解。
