| Enteropathogenic E. coli non-LEE encoded effectors NleH1 and NleH2 attenuate NF-κB activation. | |
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MedLine Citation:
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PMID: 21091507 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enteric bacterial pathogens have evolved sophisticated strategies to evade host immune defences. Some pathogens deliver anti-inflammatory effector molecules into the host cell cytoplasm via a type III secretion system (T3SS). Enteropathogenic Escherichia coli (EPEC) inhibits inflammation by an undefined, T3SS-dependent mechanism. Two proteins encoded outside of the EPEC locus of enterocyte effacement (LEE) pathogenicity island, non-LEE-encoded effector H1 (NleH1) and H2 (NleH2), display sequence similarity to Shigella flexneri OspG, which inhibits activation of the pro-inflammatory transcription factor NF-κB. We hypothesized that the anti-inflammatory effects of EPEC were mediated by NleH1 and NleH2. In this study, we examined the effect of NleH1/H2 on the NF-κB pathway. We show that NleH1/H2 are secreted via the T3SS and that transfection of cells with plasmids harbouring nleH1 or nleH2 decreased IKK-β-induced NF-κB activity and attenuated TNF-α-induced degradation of phospho-IκBα by preventing ubiquitination. Serum KC levels were higher in mice infected with ΔnleH1H2 than those infected with WT EPEC, indicating that NleH1/H2 dampen pro-inflammatory cytokine expression. ΔnleH1H2 was cleared more rapidly than WT EPEC while complementation of ΔnleH1H2 with either NleH1 or NleH2 prolonged colonization. Together, these data show that NleH1 and NleH2 function to dampen host inflammation and facilitate EPEC colonization during pathogenesis. |
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Authors:
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Sandhya V Royan; Rheinallt M Jones; Athanasia Koutsouris; Jennifer L Roxas; Kanakeshwari Falzari; Andrew W Weflen; Amy Kim; Amy Bellmeyer; Jerrold R Turner; Andrew S Neish; Ki-Jong Rhee; V K Viswanathan; Gail A Hecht |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-15 |
Journal Detail:
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Title: Molecular microbiology Volume: 78 ISSN: 1365-2958 ISO Abbreviation: Mol. Microbiol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-03-10 Revised Date: 2012-04-18 |
Medline Journal Info:
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Nlm Unique ID: 8712028 Medline TA: Mol Microbiol Country: England |
Other Details:
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Languages: eng Pagination: 1232-45 Citation Subset: IM |
Copyright Information:
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© 2010 Blackwell Publishing Ltd. |
Affiliation:
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Department of Medicine, Section of Digestive Diseases and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Enteropathogenic Escherichia coli / genetics, immunology* Escherichia coli Infections / genetics, immunology*, microbiology Escherichia coli Proteins / genetics, immunology* HEK293 Cells Humans I-kappa B Proteins / genetics, immunology Male Mice Mice, Inbred C57BL NF-kappa B / genetics, immunology* |
| Grant Support | |
ID/Acronym/Agency:
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K01 DK081481/DK/NIDDK NIH HHS; P01 DK067887/DK/NIDDK NIH HHS; P01 DK067887-04/DK/NIDDK NIH HHS; P01 DK067887-04S1/DK/NIDDK NIH HHS; P01 DK067887-05/DK/NIDDK NIH HHS; R01 DK050694/DK/NIDDK NIH HHS; R01 DK050694-13/DK/NIDDK NIH HHS; R01 DK050694-14/DK/NIDDK NIH HHS; R01 DK058964-08/DK/NIDDK NIH HHS; R01 DK058964-09/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Escherichia coli Proteins; 0/I-kappa B Proteins; 0/NF-kappa B; 139874-52-5/NF-kappaB inhibitor alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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