PMID- 33691113
OWN - NLM
STAT- MEDLINE
DCOM- 20220125
LR  - 20220125
IS  - 2211-1247 (Electronic)
VI  - 34
IP  - 10
DP  - 2021 Mar 9
TI  - Bacterial infection reinforces host metabolic flux from arginine to spermine for 
      NLRP3 inflammasome evasion.
PG  - 108832
LID - S2211-1247(21)00146-7 [pii]
LID - 10.1016/j.celrep.2021.108832 [doi]
AB  - 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 inhibits K(+) efflux-dependent NLRP3 inflammasome activation. 
      These data highlight the mechanism of bacterial gene-mediated arginine metabolism 
      control for NLRP3 inflammasome evasion.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Jiang, Jiatiao
AU  - Jiang J
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China.
FAU - Wang, Wenwen
AU  - Wang W
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China.
FAU - Sun, Fei
AU  - Sun F
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China.
FAU - Zhang, Yuanxing
AU  - Zhang Y
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China; Southern Marine Science and Engineering 
      Guangdong Laboratory (Zhuhai), Zhuhai 519000, China.
FAU - Liu, Qin
AU  - Liu Q
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China; Laboratory for Marine Biology and 
      Biotechnology, Qingdao National Laboratory for Marine Science and Technology, 
      Qingdao 266071, China; Shanghai Engineering Research Center of Maricultured 
      Animal Vaccines, Shanghai 200237, China.
FAU - Yang, Dahai
AU  - Yang D
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of 
      Maricultured Animal Vaccines, Shanghai 200237, China. Electronic address: 
      dahaiyang@ecust.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Calcium Channels)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Ipaf protein, mouse)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Organic Cation Transporter 2)
RN  - 0 (Potassium-Hydrogen Antiporters)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Trpv6 protein, mouse)
RN  - 2FZ7Y3VOQX (Spermine)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - Edwardsiella piscicida
SB  - IM
MH  - Animals
MH  - Apoptosis Regulatory Proteins/deficiency/genetics
MH  - Arginine/*metabolism
MH  - Calcium Channels/genetics/metabolism
MH  - Calcium-Binding Proteins/deficiency/genetics
MH  - Caspase 1/metabolism
MH  - Edwardsiella/immunology/*physiology
MH  - Female
MH  - Inflammasomes/*metabolism
MH  - Interleukin-1beta/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/cytology/drug effects/metabolism/microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & 
      inhibitors/*metabolism
MH  - Organic Cation Transporter 2/genetics/metabolism
MH  - Potassium-Hydrogen Antiporters/metabolism
MH  - Spermine/*metabolism
MH  - TRPV Cation Channels/antagonists & inhibitors/genetics/metabolism
OTO - NOTNLM
OT  - Edwardsiella piscicida
OT  - K(+) efflux
OT  - NLRP3 inflammasome
OT  - arginine metabolism
OT  - spermine
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2021/03/11 06:00
MHDA- 2022/01/27 06:00
CRDT- 2021/03/10 20:08
PHST- 2020/09/10 00:00 [received]
PHST- 2021/01/11 00:00 [revised]
PHST- 2021/02/16 00:00 [accepted]
PHST- 2021/03/10 20:08 [entrez]
PHST- 2021/03/11 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
AID - S2211-1247(21)00146-7 [pii]
AID - 10.1016/j.celrep.2021.108832 [doi]
PST - ppublish
SO  - Cell Rep. 2021 Mar 9;34(10):108832. doi: 10.1016/j.celrep.2021.108832.