Histamine activates HinK to promote the virulence of Pseudomonas aeruginosa

• 作者: Yaya Wang Qiao Cao Qin Cao Jianhua Gan Ning Sun Cai-Guang Yang Taeok Bae Min Wu Lefu Lan
• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2021,（11）
• 所属期刊栏目: ARTICLES
• 页码范围: 1101-1118
• 页数: 18页
• 语种: 英文

摘要

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 transcrip-tional 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 tran-scriptional 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 patho-genic bacteria to exploit host regulatory signals to promote virulence.