文献类型：期刊文献

英文题名：Bacterial infection reinforces host metabolic flux from arginine to spermine for NLRP3 inflammasome evasion

作者：Jiang, Jiatiao[1];Wang, Wenwen[1];Sun, Fei[1];Zhang, Yuanxing[1,2];Liu, Qin[1,3,4];Yang, Dahai[1,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Southern Marine Sci & Engn Guangdong Lab Zhuhai, Zhuhai 519000, Peoples R China;[3]Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao 266071, Peoples R China;[4]Shanghai Engn Res Ctr Maricultured Anim Vaccines, Shanghai 200237, Peoples R China

年份：2021

卷号：34

期号：10

外文期刊名：CELL REPORTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000627660900019)】；

基金：WewouldliketothankDr. FengShaofromNIBsforprovidingcasp1-/- casp11-/-, nlrp3-/-, and nlrc4-/- mice. This work was supported by National Key Research and Development Program of China 2018YFC0311300 (toQ.L.), National Natural Science Foundation of China 32025038 (toQ.L.), and the Science and Technology Innovation Program by STCSM 20ZR1415500 (to D.Y.).

语种：英文

摘要：Hosts recognize cytosolic microbial infection via the nucleotide-binding domain-like receptor (NLR) protein family, triggering inflammasome complex assembly to provoke pyroptosis or cytokine-related caspase-1-dependent antimicrobial responses. Pathogens have evolved diverse strategies to antagonize inflammasome activation. Here, Edwardsiella piscicida gene-defined transposon library screening for lactate dehydrogenase (LDH) release in nlrc4(-/-) bone marrow-derived macrophages (BMDMs) demonstrates that genes clustered in the bacterial arginine metabolism pathway participate in NLRP3 inflammasome inhibition. Blocking arginine uptake or putrescine export significantly relieves NLRP3 inflammasome inhibition, indicating that this bacterium rewires its arginine metabolism network during infection. Moreover, intracellular E. piscicida recruits the host arginine importer (mCAT-1) and putrescine exporter (Oct-2) to bacterium-containing vacuoles, accompanied by reduced arginine and accumulated cytosolic spermine. Neutralizing E. piscicida-induced cytosolic spermine enhancement by spermine synthetase or extracellular spermine significantly alters NLRP3 inflammasome activation. Importantly, accumulated cytosolic spermine inhibitsK(+) efflux-dependent NLRP3 inflammasome activation. These data highlight the mechanism of bacterial gene-mediated arginine metabolism control for NLRP3 inflammasome evasion.