內源性大麻素抑制腸道致病菌毒力誘導
作者:
小柯機器人發布時間:2020/10/10 14:52:13
美國UT西南醫學中心Vanessa Sperandio研究組發現內源性大麻素抑制腸道病原體中毒力誘導。相關論文於2020年10月7日發表於國際頂尖學術期刊《細胞》。
他們顯示具有高水平的內源性大麻素2-花生四烯醯基甘油(2-AG)的小鼠受到腸桿菌科病原體腸道感染的保護。2-AG通過抑制感染成功必不可少的毒力程序來直接調節病原體功能。此外,2-AG拮抗細菌受體QseC,QseC是在腸桿菌科細菌的核心基因組內編碼的組氨酸激酶,可促進與病原體相關的三型分泌系統的激活。綜上所述,他們的發現確定細菌可以直接感知內源性大麻素,並且可以調節細菌的功能。
據介紹,內源性大麻素是源自宿主的脂質激素,從根本上影響胃腸道(GI)生物學。大麻和其他內源性大麻素作為各種胃腸道疾病的獨特治療方法的使用,激發了對這些化合物介導其作用的機制的探索,從而發現了哺乳動物的內源性大麻素系統。內源性大麻素信號失調與炎症和腸道菌群有關。但是,尚未探討內源性大麻素對宿主感染的易感性的影響。
附:英文原文
Title: Endocannabinoids Inhibit the Induction of Virulence in Enteric Pathogens
Author: Melissa Ellermann, Alline R. Pacheco, Angel G. Jimenez, Regan M. Russell, Santiago Cuesta, Aman Kumar, Wenhan Zhu, Gonalo Vale, Sarah A. Martin, Prithvi Raj, Jeffrey G. McDonald, Sebastian E. Winter, Vanessa Sperandio
Issue&Volume: 2020-10-07
Abstract: Endocannabinoids are host-derived lipid hormones that fundamentally impact gastrointestinal(GI) biology. The use of cannabis and other exocannabinoids as anecdotal treatmentsfor various GI disorders inspired the search for mechanisms by which these compoundsmediate their effects, which led to the discovery of the mammalian endocannabinoidsystem. Dysregulated endocannabinoid signaling was linked to inflammation and thegut microbiota. However, the effects of endocannabinoids on host susceptibility toinfection has not been explored. Here, we show that mice with elevated levels of theendocannabinoid 2-arachidonoyl glycerol (2-AG) are protected from enteric infectionby Enterobacteriaceae pathogens. 2-AG directly modulates pathogen function by inhibitingvirulence programs essential for successful infection. Furthermore, 2-AG antagonizesthe bacterial receptor QseC, a histidine kinase encoded within the core Enterobacteriaceaegenome that promotes the activation of pathogen-associated type three secretion systems.Taken together, our findings establish that endocannabinoids are directly sensed bybacteria and can modulate bacterial function.
DOI: 10.1016/j.cell.2020.09.022
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31163-6
Cell:《細胞》,創刊於1974年。隸屬於細胞出版社,最新IF:36.216