skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter

Abstract

Many pathogenic bacteria of the familyEnterobacteriaceaeuse type III secretion systems to inject virulence proteins, termed “effectors,” into the host cell cytosol. Although host-cellular activities of several effectors have been demonstrated, the function and host-targeted pathways of most of the effectors identified to date are largely undetermined. To gain insight into host proteins targeted by bacterial effectors, we performed coaffinity purification of host proteins from cell lysates using recombinant effectors from theEnterobacteriaceaeintracellular pathogensSalmonella entericaserovar Typhimurium andCitrobacter rodentium. We identified 54 high-confidence host interactors for theSalmonellaeffectors GogA, GtgA, GtgE, SpvC, SrfH, SseL, SspH1, and SssB collectively and 21 interactors for theCitrobactereffectors EspT, NleA, NleG1, and NleK. We biochemically validated the interaction between the SrfHSalmonellaprotein and the extracellular signal-regulated kinase 2 (ERK2) host protein kinase, which revealed a role for this effector in regulating phosphorylation levels of this enzyme, which plays a central role in signal transduction. IMPORTANCEDuring infection, pathogenic bacteria face an adverse environment of factors driven by both cellular and humoral defense mechanisms. To help evade the immune response and ultimately proliferate inside the host, many bacteria evolved specialized secretion systems to deliver effector proteins directly into host cells. Translocated effector proteins function to subvert host defense mechanisms. Numerous pathogenic bacteriamore » use a specialized secretion system called type III secretion to deliver effectors into the host cell cytosol. Here, we identified 75 new host targets ofSalmonellaandCitrobactereffectors, which will help elucidate their mechanisms of action.« less

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1342323
Report Number(s):
PNNL-SA-114706
Journal ID: ISSN 2379-5077; 400412000
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
mSystems
Additional Journal Information:
Journal Volume: 1; Journal Issue: 4; Journal ID: ISSN 2379-5077
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Sontag, Ryan L., Nakayasu, Ernesto S., Brown, Roslyn N., Niemann, George S., Sydor, Michael A., Sanchez, Octavio, Ansong, Charles, Lu, Shao-Yeh, Choi, Hyungwon, Valleau, Dylan, Weitz, Karl K., Savchenko, Alexei, Cambronne, Eric D., Adkins, Joshua N., and McFall-Ngai, Margaret J. Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter. United States: N. p., 2016. Web. doi:10.1128/mSystems.00032-15.
Sontag, Ryan L., Nakayasu, Ernesto S., Brown, Roslyn N., Niemann, George S., Sydor, Michael A., Sanchez, Octavio, Ansong, Charles, Lu, Shao-Yeh, Choi, Hyungwon, Valleau, Dylan, Weitz, Karl K., Savchenko, Alexei, Cambronne, Eric D., Adkins, Joshua N., & McFall-Ngai, Margaret J. Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter. United States. doi:10.1128/mSystems.00032-15.
Sontag, Ryan L., Nakayasu, Ernesto S., Brown, Roslyn N., Niemann, George S., Sydor, Michael A., Sanchez, Octavio, Ansong, Charles, Lu, Shao-Yeh, Choi, Hyungwon, Valleau, Dylan, Weitz, Karl K., Savchenko, Alexei, Cambronne, Eric D., Adkins, Joshua N., and McFall-Ngai, Margaret J. Tue . "Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter". United States. doi:10.1128/mSystems.00032-15.
@article{osti_1342323,
title = {Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter},
author = {Sontag, Ryan L. and Nakayasu, Ernesto S. and Brown, Roslyn N. and Niemann, George S. and Sydor, Michael A. and Sanchez, Octavio and Ansong, Charles and Lu, Shao-Yeh and Choi, Hyungwon and Valleau, Dylan and Weitz, Karl K. and Savchenko, Alexei and Cambronne, Eric D. and Adkins, Joshua N. and McFall-Ngai, Margaret J.},
abstractNote = {Many pathogenic bacteria of the familyEnterobacteriaceaeuse type III secretion systems to inject virulence proteins, termed “effectors,” into the host cell cytosol. Although host-cellular activities of several effectors have been demonstrated, the function and host-targeted pathways of most of the effectors identified to date are largely undetermined. To gain insight into host proteins targeted by bacterial effectors, we performed coaffinity purification of host proteins from cell lysates using recombinant effectors from theEnterobacteriaceaeintracellular pathogensSalmonella entericaserovar Typhimurium andCitrobacter rodentium. We identified 54 high-confidence host interactors for theSalmonellaeffectors GogA, GtgA, GtgE, SpvC, SrfH, SseL, SspH1, and SssB collectively and 21 interactors for theCitrobactereffectors EspT, NleA, NleG1, and NleK. We biochemically validated the interaction between the SrfHSalmonellaprotein and the extracellular signal-regulated kinase 2 (ERK2) host protein kinase, which revealed a role for this effector in regulating phosphorylation levels of this enzyme, which plays a central role in signal transduction. IMPORTANCEDuring infection, pathogenic bacteria face an adverse environment of factors driven by both cellular and humoral defense mechanisms. To help evade the immune response and ultimately proliferate inside the host, many bacteria evolved specialized secretion systems to deliver effector proteins directly into host cells. Translocated effector proteins function to subvert host defense mechanisms. Numerous pathogenic bacteria use a specialized secretion system called type III secretion to deliver effectors into the host cell cytosol. Here, we identified 75 new host targets ofSalmonellaandCitrobactereffectors, which will help elucidate their mechanisms of action.},
doi = {10.1128/mSystems.00032-15},
journal = {mSystems},
issn = {2379-5077},
number = 4,
volume = 1,
place = {United States},
year = {2016},
month = {7}
}