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 ...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 Lys R-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(Im AA),a histamine metabolite whose production in P.aeruginosa depends on the HinK-activated histamine uptake and utilization operon hin DAC-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.展开更多
基金supported by the Ministry of Science and Technology(MOST)of China(2016YFA0501503 and 2019ZX09721001-004-003)the National Natural Science Foundation of China(31670136,31870127,and 81861138047)+1 种基金the Science and Technology Commission of Shanghai Municipality(19JC1416400)the State Key Laboratory of Drug Research(SIMM2003ZZ-03)。
文摘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 Lys R-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(Im AA),a histamine metabolite whose production in P.aeruginosa depends on the HinK-activated histamine uptake and utilization operon hin DAC-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.
