PMID- 24439371
OWN - NLM
STAT- MEDLINE
DCOM- 20140407
LR  - 20220330
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 156
IP  - 1-2
DP  - 2014 Jan 16
TI  - An extracellular bacterial pathogen modulates host metabolism to regulate its own 
      sensing and proliferation.
PG  - 97-108
LID - S0092-8674(13)01539-0 [pii]
LID - 10.1016/j.cell.2013.12.007 [doi]
AB  - Successful infection depends on the ability of the pathogen to gain nutrients 
      from the host. The extracellular pathogenic bacterium group A Streptococcus (GAS) 
      causes a vast array of human diseases. By using the quorum-sensing sil system as 
      a reporter, we found that, during adherence to host cells, GAS delivers 
      streptolysin toxins, creating endoplasmic reticulum stress. This, in turn, 
      increases asparagine (ASN) synthetase expression and the production of ASN. The 
      released ASN is sensed by the bacteria, altering the expression of  approximately 17% of GAS 
      genes of which about one-third are dependent on the two-component system TrxSR. 
      The expression of the streptolysin toxins is strongly upregulated, whereas genes 
      linked to proliferation are downregulated in ASN absence. Asparaginase, a widely 
      used chemotherapeutic agent, arrests GAS growth in human blood and blocks GAS 
      proliferation in a mouse model of human bacteremia. These results delineate a 
      pathogenic pathway and propose a therapeutic strategy against GAS infections.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Baruch, Moshe
AU  - Baruch M
AD  - Department of Microbiology and Molecular Genetics, The Hebrew University of 
      Jerusalem, Faculty of Medicine, Jerusalem 91120, Israel.
FAU - Belotserkovsky, Ilia
AU  - Belotserkovsky I
AD  - Department of Microbiology and Molecular Genetics, The Hebrew University of 
      Jerusalem, Faculty of Medicine, Jerusalem 91120, Israel.
FAU - Hertzog, Baruch B
AU  - Hertzog BB
AD  - Department of Microbiology and Molecular Genetics, The Hebrew University of 
      Jerusalem, Faculty of Medicine, Jerusalem 91120, Israel.
FAU - Ravins, Miriam
AU  - Ravins M
AD  - Department of Microbiology and Molecular Genetics, The Hebrew University of 
      Jerusalem, Faculty of Medicine, Jerusalem 91120, Israel.
FAU - Dov, Eran
AU  - Dov E
AD  - Department of Microbiology and Molecular Genetics, The Hebrew University of 
      Jerusalem, Faculty of Medicine, Jerusalem 91120, Israel.
FAU - McIver, Kevin S
AU  - McIver KS
AD  - Department of Cell Biology & Molecular Genetics and Maryland Pathogen Research 
      Institut, University of Maryland, College Park, MD 20742, USA.
FAU - Le Breton, Yoann S
AU  - Le Breton YS
AD  - Department of Cell Biology & Molecular Genetics and Maryland Pathogen Research 
      Institut, University of Maryland, College Park, MD 20742, USA.
FAU - Zhou, Yiting
AU  - Zhou Y
AD  - Mechanism of Inflammation Program, Center for Research Excellence & Technological 
      Enterprise (CREATE), National University of Singapore and The Hebrew University 
      of Jerusalem (HUJI), Singapore 138602, Singapore.
FAU - Cheng, Catherine Youting
AU  - Cheng CY
AD  - Mechanism of Inflammation Program, Center for Research Excellence & Technological 
      Enterprise (CREATE), National University of Singapore and The Hebrew University 
      of Jerusalem (HUJI), Singapore 138602, Singapore.
FAU - Hanski, Emanuel
AU  - Hanski E
AD  - Department of Microbiology and Molecular Genetics, The Hebrew University of 
      Jerusalem, Faculty of Medicine, Jerusalem 91120, Israel; Mechanism of 
      Inflammation Program, Center for Research Excellence & Technological Enterprise 
      (CREATE), National University of Singapore and The Hebrew University of Jerusalem 
      (HUJI), Singapore 138602, Singapore. Electronic address: 
      emanuelh@ekmd.huji.ac.il.
LA  - eng
SI  - SRA/PRJNA2188-56
GR  - R01 AI047928/AI/NIAID NIH HHS/United States
GR  - AI47928/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Virulence Factors)
RN  - 7006-34-0 (Asparagine)
RN  - EC 6.3.1.1 (Aspartate-Ammonia Ligase)
SB  - IM
EIN - Cell. 2014 Jan 30;156(3):617. Chen, Catherine Youting [corrected to Cheng, 
      Catherine Youting]
CIN - Nat Rev Microbiol. 2014 Mar;12(3):154. PMID: 24525876
MH  - Animals
MH  - Asparagine/metabolism
MH  - Aspartate-Ammonia Ligase/genetics/metabolism
MH  - Bacteremia/microbiology
MH  - Disease Models, Animal
MH  - Endoplasmic Reticulum Stress
MH  - HeLa Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *Quorum Sensing
MH  - Streptococcal Infections/*microbiology
MH  - Streptococcus/cytology/*metabolism/pathogenicity
MH  - Transcription, Genetic
MH  - Virulence Factors/genetics
PMC - PMC3926133
MID - NIHMS548314
EDAT- 2014/01/21 06:00
MHDA- 2014/04/08 06:00
PMCR- 2015/01/16
CRDT- 2014/01/21 06:00
PHST- 2013/02/19 00:00 [received]
PHST- 2013/09/16 00:00 [revised]
PHST- 2013/11/15 00:00 [accepted]
PHST- 2014/01/21 06:00 [entrez]
PHST- 2014/01/21 06:00 [pubmed]
PHST- 2014/04/08 06:00 [medline]
PHST- 2015/01/16 00:00 [pmc-release]
AID - S0092-8674(13)01539-0 [pii]
AID - 10.1016/j.cell.2013.12.007 [doi]
PST - ppublish
SO  - Cell. 2014 Jan 16;156(1-2):97-108. doi: 10.1016/j.cell.2013.12.007.