PMID- 24835993
OWN - NLM
STAT- MEDLINE
DCOM- 20150821
LR  - 20170913
IS  - 2211-1247 (Electronic)
VI  - 7
IP  - 5
DP  - 2014 Jun 12
TI  - The central metabolism regulator EIIAGlc switches Salmonella from growth arrest 
      to acute virulence through activation of virulence factor secretion.
PG  - 1426-1433
LID - S2211-1247(14)00324-6 [pii]
LID - 10.1016/j.celrep.2014.04.022 [doi]
AB  - The ability of Salmonella to cause disease depends on metabolic activities and 
      virulence factors. Here, we show that a key metabolic protein, EIIAGlc, is 
      absolutely essential for acute infection, but not for Salmonella survival, in a 
      mouse typhoid fever model. Surprisingly, phosphorylation-dependent EIIAGlc 
      functions, including carbohydrate transport and activation of adenylate cyclase 
      for global regulation, do not explain this virulence phenotype. Instead, 
      biochemical studies, in vitro secretion and translocation assays, and in vivo 
      genetic epistasis experiments suggest that EIIAGlc binds to the type three 
      secretion system 2 (TTSS-2) involved in systemic virulence, stabilizes its 
      cytoplasmic part including the crucial TTSS-2 ATPase, and activates virulence 
      factor secretion. This unexpected role of EIIAGlc reveals a striking direct link 
      between central Salmonella metabolism and a crucial virulence mechanism.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Maze, Alain
AU  - Maze A
AD  - Focal Area Infection Biology, Biozentrum, University of Basel, 4056 Basel, 
      Switzerland; Synthetic Biology, UMR7242, ESBS, University of Strasbourg, 67412 
      Illkirch, France.
FAU - Glatter, Timo
AU  - Glatter T
AD  - Proteomics Core Facility, Biozentrum, University of Basel, 4056 Basel, 
      Switzerland.
FAU - Bumann, Dirk
AU  - Bumann D
AD  - Focal Area Infection Biology, Biozentrum, University of Basel, 4056 Basel, 
      Switzerland. Electronic address: dirk.bumann@unibas.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140515
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Bacterial Proteins)
RN  - 0 (Virulence Factors)
RN  - EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
SB  - IM
MH  - Adenylyl Cyclases/metabolism
MH  - Animals
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Carbohydrate Metabolism
MH  - Epistasis, Genetic
MH  - Mice
MH  - Phosphoenolpyruvate Sugar Phosphotransferase System/genetics/*metabolism
MH  - Protein Binding
MH  - Salmonella typhimurium/growth & development/metabolism/*pathogenicity
MH  - Typhoid Fever/microbiology
MH  - Virulence Factors/genetics/*metabolism
EDAT- 2014/05/20 06:00
MHDA- 2015/08/22 06:00
CRDT- 2014/05/20 06:00
PHST- 2013/08/14 00:00 [received]
PHST- 2014/03/07 00:00 [revised]
PHST- 2014/04/14 00:00 [accepted]
PHST- 2014/05/20 06:00 [entrez]
PHST- 2014/05/20 06:00 [pubmed]
PHST- 2015/08/22 06:00 [medline]
AID - S2211-1247(14)00324-6 [pii]
AID - 10.1016/j.celrep.2014.04.022 [doi]
PST - ppublish
SO  - Cell Rep. 2014 Jun 12;7(5):1426-1433. doi: 10.1016/j.celrep.2014.04.022. Epub 
      2014 May 15.