@article{e0cdab75b77e4ab0a73337484622dcf6,
title = "Endocannabinoids Inhibit the Induction of Virulence in Enteric Pathogens",
abstract = "Endocannabinoids are host-derived lipid hormones that fundamentally impact gastrointestinal (GI) biology. The use of cannabis and other exocannabinoids as anecdotal treatments for various GI disorders inspired the search for mechanisms by which these compounds mediate their effects, which led to the discovery of the mammalian endocannabinoid system. Dysregulated endocannabinoid signaling was linked to inflammation and the gut microbiota. However, the effects of endocannabinoids on host susceptibility to infection has not been explored. Here, we show that mice with elevated levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG) are protected from enteric infection by Enterobacteriaceae pathogens. 2-AG directly modulates pathogen function by inhibiting virulence programs essential for successful infection. Furthermore, 2-AG antagonizes the bacterial receptor QseC, a histidine kinase encoded within the core Enterobacteriaceae genome that promotes the activation of pathogen-associated type three secretion systems. Taken together, our findings establish that endocannabinoids are directly sensed by bacteria and can modulate bacterial function.",
keywords = "2-AG, 2-arachidonoyl glycerol, Citrobacter rodentium, EHEC, QseC, Salmonella enterica, endocannabinoids, enterohemorrhagic E. coli, gut-brain axis, locus of enterocyte effacement, type three secretion system",
author = "Melissa Ellermann and Pacheco, {Alline R.} and Jimenez, {Angel G.} and Russell, {Regan M.} and Santiago Cuesta and Aman Kumar and Wenhan Zhu and Gon{\c c}alo Vale and Martin, {Sarah A.} and Prithvi Raj and McDonald, {Jeffrey G.} and Winter, {Sebastian E.} and Vanessa Sperandio",
note = "Funding Information: We thank Michael Brown and David Russell at UTSW for reviewing this manuscript. We thank Lora Hooper at UTSW for help with the germ-free experiments and reviewing this manuscript. We acknowledge the Texas A&M Institute for Genomic Medicine for the Mgll +/− breeding pairs, the UTSW Live Cell Imaging Core for confocal microscopy, the UTSW Histopathology Core for assisting with sample preparation, the UTSW Genomics and Microarray Core for RNA-seq library preparation and sequencing, the UTSW Microbiome Research Laboratory for 16S rRNA sequencing services and analysis, and Raechel Chanin for experimental help. This study was supported by the NIH grants AI053067 , AI05135 , AI077613 , and AI114511 to V.S. A.G.J. was supported through NIH training grant 5 T32 AI7520-14 . Funding Information: We thank Michael Brown and David Russell at UTSW for reviewing this manuscript. We thank Lora Hooper at UTSW for help with the germ-free experiments and reviewing this manuscript. We acknowledge the Texas A&M Institute for Genomic Medicine for the Mgll+/? breeding pairs, the UTSW Live Cell Imaging Core for confocal microscopy, the UTSW Histopathology Core for assisting with sample preparation, the UTSW Genomics and Microarray Core for RNA-seq library preparation and sequencing, the UTSW Microbiome Research Laboratory for 16S rRNA sequencing services and analysis, and Raechel Chanin for experimental help. This study was supported by the NIH grants AI053067, AI05135, AI077613, and AI114511 to V.S. A.G.J. was supported through NIH training grant 5 T32 AI7520-14. M.E. designed and conducted experiments and wrote the paper, A.R.P. designed and conducted experiments, A.G.J. R.M.R. A.K. and S.C. conducted experiments, W.Z. analyzed data, G.V. S.A.M. and P.J. conducted experiments and analyzed data, J.G.M. designed experiments, S.E.W. analyzed data, and V.S. supervised all experiments, analyzed data, and wrote the paper. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = oct,
day = "29",
doi = "10.1016/j.cell.2020.09.022",
language = "English (US)",
volume = "183",
pages = "650--665.e15",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}