Identification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>

ABSTRACT Many pathogenic bacteria of the family Enterobacteriaceae use 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 mo...

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Autores principales:	Ryan L. Sontag, Ernesto S. Nakayasu, Roslyn N. Brown, George S. Niemann, Michael A. Sydor, Octavio Sanchez, Charles Ansong, Shao-Yeh Lu, Hyungwon Choi, Dylan Valleau, Karl K. Weitz, Alexei Savchenko, Eric D. Cambronne, Joshua N. Adkins
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	affinity purification mass spectrometry effectors pathogenic bacteria type III secretion system protein-protein interactions Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f78a2ab44ff5495684196c96fa5db218
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spelling	oai:doaj.org-article:f78a2ab44ff5495684196c96fa5db2182021-12-02T19:45:29ZIdentification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>10.1128/mSystems.00032-152379-5077https://doaj.org/article/f78a2ab44ff5495684196c96fa5db2182016-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00032-15https://doaj.org/toc/2379-5077ABSTRACT Many pathogenic bacteria of the family Enterobacteriaceae use 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 the Enterobacteriaceae intracellular pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium. We identified 54 high-confidence host interactors for the Salmonella effectors GogA, GtgA, GtgE, SpvC, SrfH, SseL, SspH1, and SssB collectively and 21 interactors for the Citrobacter effectors EspT, NleA, NleG1, and NleK. We biochemically validated the interaction between the SrfH Salmonella protein 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. IMPORTANCE During 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 of Salmonella and Citrobacter effectors, which will help elucidate their mechanisms of action.Ryan L. SontagErnesto S. NakayasuRoslyn N. BrownGeorge S. NiemannMichael A. SydorOctavio SanchezCharles AnsongShao-Yeh LuHyungwon ChoiDylan ValleauKarl K. WeitzAlexei SavchenkoEric D. CambronneJoshua N. AdkinsAmerican Society for Microbiologyarticleaffinity purificationmass spectrometryeffectorspathogenic bacteriatype III secretion systemprotein-protein interactionsMicrobiologyQR1-502ENmSystems, Vol 1, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	affinity purification mass spectrometry effectors pathogenic bacteria type III secretion system protein-protein interactions Microbiology QR1-502
spellingShingle	affinity purification mass spectrometry effectors pathogenic bacteria type III secretion system protein-protein interactions Microbiology QR1-502 Ryan L. Sontag Ernesto S. Nakayasu Roslyn N. Brown George S. Niemann Michael A. Sydor Octavio Sanchez Charles Ansong Shao-Yeh Lu Hyungwon Choi Dylan Valleau Karl K. Weitz Alexei Savchenko Eric D. Cambronne Joshua N. Adkins Identification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>
description	ABSTRACT Many pathogenic bacteria of the family Enterobacteriaceae use 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 the Enterobacteriaceae intracellular pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium. We identified 54 high-confidence host interactors for the Salmonella effectors GogA, GtgA, GtgE, SpvC, SrfH, SseL, SspH1, and SssB collectively and 21 interactors for the Citrobacter effectors EspT, NleA, NleG1, and NleK. We biochemically validated the interaction between the SrfH Salmonella protein 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. IMPORTANCE During 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 of Salmonella and Citrobacter effectors, which will help elucidate their mechanisms of action.
format	article
author	Ryan L. Sontag Ernesto S. Nakayasu Roslyn N. Brown George S. Niemann Michael A. Sydor Octavio Sanchez Charles Ansong Shao-Yeh Lu Hyungwon Choi Dylan Valleau Karl K. Weitz Alexei Savchenko Eric D. Cambronne Joshua N. Adkins
author_facet	Ryan L. Sontag Ernesto S. Nakayasu Roslyn N. Brown George S. Niemann Michael A. Sydor Octavio Sanchez Charles Ansong Shao-Yeh Lu Hyungwon Choi Dylan Valleau Karl K. Weitz Alexei Savchenko Eric D. Cambronne Joshua N. Adkins
author_sort	Ryan L. Sontag
title	Identification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>
title_short	Identification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>
title_full	Identification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>
title_fullStr	Identification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>
title_full_unstemmed	Identification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>
title_sort	identification of novel host interactors of effectors secreted by <italic toggle="yes">salmonella</italic> and <italic toggle="yes">citrobacter</italic>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/f78a2ab44ff5495684196c96fa5db218
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Identification of Novel Host Interactors of Effectors Secreted by <italic toggle="yes">Salmonella</italic> and <italic toggle="yes">Citrobacter</italic>

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