Distinct roles of the antiapoptotic effectors NleB and NleF from enteropathogenic Escherichia coli

Georgina L. Pollock, Clare V.L. Oates, Cristina Giogha, Tania Wong Fok Lung, Sze Ying Ong, Jaclyn S. Pearson, Elizabeth L. Hartland

Research output: Contribution to journalArticleResearchpeer-review

Abstract

During infection, enteropathogenic Escherichia coli (EPEC) translocates effector proteins directly into the cytosol of infected enterocytes using a type III secretion system (T3SS). Once inside the host cell, these effector proteins subvert various immune signaling pathways, including death receptor-induced apoptosis. One such effector protein is the non-locus of enterocyte effacement (LEE)-encoded effector NleB1, which inhibits extrinsic apoptotic signaling via the FAS death receptor. NleB1 transfers a single N-acetylglucosamine (GlcNAc) residue to Arg117 in the death domain of Fas-associated protein with death domain (FADD) and inhibits FAS ligand (FasL)-stimulated caspase-8 cleavage. Another effector secreted by the T3SS is NleF. Previous studies have shown that NleF binds to and inhibits the activity of caspase-4, -8, and -9 in vitro. Here, we investigated a role for NleF in the inhibition of FAS signaling and apoptosis during EPEC infection. We show that NleF prevents the cleavage of caspase-8, caspase-3, and receptor-interacting serine/ threonine protein kinase 1 (RIPK1) in response to FasL stimulation. When translocated into host cells by the T3SS or expressed ectopically, NleF also blocked FasL-induced cell death. Using the EPEC-like mouse pathogen Citrobacter rodentium, we found that NleB but not NleF contributed to colonization of mice in the intestine. Hence, despite their shared ability to block FasL/FAS signaling, NleB and NleF have distinct roles during infection.

Original languageEnglish
Article numbere01071-16
Number of pages12
JournalInfection and Immunity
Volume85
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017
Externally publishedYes

Keywords

  • Caspase inhibitor
  • Cell death
  • EPEC
  • FasL signaling
  • NleB1
  • NleF

Cite this

Pollock, Georgina L. ; Oates, Clare V.L. ; Giogha, Cristina ; Lung, Tania Wong Fok ; Ong, Sze Ying ; Pearson, Jaclyn S. ; Hartland, Elizabeth L. / Distinct roles of the antiapoptotic effectors NleB and NleF from enteropathogenic Escherichia coli. In: Infection and Immunity. 2017 ; Vol. 85, No. 4.
@article{33465653575c47078c19211b57271ad6,
title = "Distinct roles of the antiapoptotic effectors NleB and NleF from enteropathogenic Escherichia coli",
abstract = "During infection, enteropathogenic Escherichia coli (EPEC) translocates effector proteins directly into the cytosol of infected enterocytes using a type III secretion system (T3SS). Once inside the host cell, these effector proteins subvert various immune signaling pathways, including death receptor-induced apoptosis. One such effector protein is the non-locus of enterocyte effacement (LEE)-encoded effector NleB1, which inhibits extrinsic apoptotic signaling via the FAS death receptor. NleB1 transfers a single N-acetylglucosamine (GlcNAc) residue to Arg117 in the death domain of Fas-associated protein with death domain (FADD) and inhibits FAS ligand (FasL)-stimulated caspase-8 cleavage. Another effector secreted by the T3SS is NleF. Previous studies have shown that NleF binds to and inhibits the activity of caspase-4, -8, and -9 in vitro. Here, we investigated a role for NleF in the inhibition of FAS signaling and apoptosis during EPEC infection. We show that NleF prevents the cleavage of caspase-8, caspase-3, and receptor-interacting serine/ threonine protein kinase 1 (RIPK1) in response to FasL stimulation. When translocated into host cells by the T3SS or expressed ectopically, NleF also blocked FasL-induced cell death. Using the EPEC-like mouse pathogen Citrobacter rodentium, we found that NleB but not NleF contributed to colonization of mice in the intestine. Hence, despite their shared ability to block FasL/FAS signaling, NleB and NleF have distinct roles during infection.",
keywords = "Caspase inhibitor, Cell death, EPEC, FasL signaling, NleB1, NleF",
author = "Pollock, {Georgina L.} and Oates, {Clare V.L.} and Cristina Giogha and Lung, {Tania Wong Fok} and Ong, {Sze Ying} and Pearson, {Jaclyn S.} and Hartland, {Elizabeth L.}",
year = "2017",
month = "4",
day = "1",
doi = "10.1128/IAI.01071-16",
language = "English",
volume = "85",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "4",

}

Distinct roles of the antiapoptotic effectors NleB and NleF from enteropathogenic Escherichia coli. / Pollock, Georgina L.; Oates, Clare V.L.; Giogha, Cristina; Lung, Tania Wong Fok; Ong, Sze Ying; Pearson, Jaclyn S.; Hartland, Elizabeth L.

In: Infection and Immunity, Vol. 85, No. 4, e01071-16, 01.04.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Distinct roles of the antiapoptotic effectors NleB and NleF from enteropathogenic Escherichia coli

AU - Pollock, Georgina L.

AU - Oates, Clare V.L.

AU - Giogha, Cristina

AU - Lung, Tania Wong Fok

AU - Ong, Sze Ying

AU - Pearson, Jaclyn S.

AU - Hartland, Elizabeth L.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - During infection, enteropathogenic Escherichia coli (EPEC) translocates effector proteins directly into the cytosol of infected enterocytes using a type III secretion system (T3SS). Once inside the host cell, these effector proteins subvert various immune signaling pathways, including death receptor-induced apoptosis. One such effector protein is the non-locus of enterocyte effacement (LEE)-encoded effector NleB1, which inhibits extrinsic apoptotic signaling via the FAS death receptor. NleB1 transfers a single N-acetylglucosamine (GlcNAc) residue to Arg117 in the death domain of Fas-associated protein with death domain (FADD) and inhibits FAS ligand (FasL)-stimulated caspase-8 cleavage. Another effector secreted by the T3SS is NleF. Previous studies have shown that NleF binds to and inhibits the activity of caspase-4, -8, and -9 in vitro. Here, we investigated a role for NleF in the inhibition of FAS signaling and apoptosis during EPEC infection. We show that NleF prevents the cleavage of caspase-8, caspase-3, and receptor-interacting serine/ threonine protein kinase 1 (RIPK1) in response to FasL stimulation. When translocated into host cells by the T3SS or expressed ectopically, NleF also blocked FasL-induced cell death. Using the EPEC-like mouse pathogen Citrobacter rodentium, we found that NleB but not NleF contributed to colonization of mice in the intestine. Hence, despite their shared ability to block FasL/FAS signaling, NleB and NleF have distinct roles during infection.

AB - During infection, enteropathogenic Escherichia coli (EPEC) translocates effector proteins directly into the cytosol of infected enterocytes using a type III secretion system (T3SS). Once inside the host cell, these effector proteins subvert various immune signaling pathways, including death receptor-induced apoptosis. One such effector protein is the non-locus of enterocyte effacement (LEE)-encoded effector NleB1, which inhibits extrinsic apoptotic signaling via the FAS death receptor. NleB1 transfers a single N-acetylglucosamine (GlcNAc) residue to Arg117 in the death domain of Fas-associated protein with death domain (FADD) and inhibits FAS ligand (FasL)-stimulated caspase-8 cleavage. Another effector secreted by the T3SS is NleF. Previous studies have shown that NleF binds to and inhibits the activity of caspase-4, -8, and -9 in vitro. Here, we investigated a role for NleF in the inhibition of FAS signaling and apoptosis during EPEC infection. We show that NleF prevents the cleavage of caspase-8, caspase-3, and receptor-interacting serine/ threonine protein kinase 1 (RIPK1) in response to FasL stimulation. When translocated into host cells by the T3SS or expressed ectopically, NleF also blocked FasL-induced cell death. Using the EPEC-like mouse pathogen Citrobacter rodentium, we found that NleB but not NleF contributed to colonization of mice in the intestine. Hence, despite their shared ability to block FasL/FAS signaling, NleB and NleF have distinct roles during infection.

KW - Caspase inhibitor

KW - Cell death

KW - EPEC

KW - FasL signaling

KW - NleB1

KW - NleF

UR - http://www.scopus.com/inward/record.url?scp=85016206721&partnerID=8YFLogxK

U2 - 10.1128/IAI.01071-16

DO - 10.1128/IAI.01071-16

M3 - Article

VL - 85

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 4

M1 - e01071-16

ER -