Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Bacterial Proteins/*metabolism ; Intestinal Mucosa/*metabolism ; MAP Kinase Kinase 4/*metabolism ; Mutant Proteins/*metabolism ; Salmonella Infections, Animal/*metabolism ; Salmonella enteritidis/*physiology ; Tight Junctions/*physiology; Animals ; Bacterial Proteins/genetics ; Colon/metabolism ; Colon/microbiology ; Female ; Humans ; Intestinal Mucosa/microbiology ; MAP Kinase Kinase 4/genetics ; Mice ; Mice, Inbred C57BL ; Mutant Proteins/genetics ; Mutation/genetics ; Salmonella Infections, Animal/microbiology ; Signal Transduction ; Tight Junctions/microbiology ; Zonula Occludens-1 Protein/genetics ; Zonula Occludens-1 Protein/metabolism
    • Abstract:
      Salmonella pathogenesis studies to date have focused on Salmonella typhimurium, and the pathogenesis of a second major serotype, Salmonella enteritidis, is poorly understood. Salmonella spp. possess effector proteins that display biochemical activities and modulate host functions. Here, we generated a deletion mutant of the effector AvrA, S.E-AvrA - , and a plasmid-mediated complementary strain, S.E-AvrA - /pAvrA + (S.E-AvrA + ), in S. Enteritidis. Using in vitro and in vivo infection models, we showed that AvrA stabilizes epithelial tight junction (TJ) proteins, such as ZO-1, in human intestinal epithelial cells. Transepithelial electrical resistance was significantly higher in cells infected with S.E-AvrA + than in cells infected with S.E-AvrA - Inhibition of the JNK pathway suppresses the disassembly of TJ proteins; we found that enteritidis AvrA inhibited JNK activity in cells infected with wild type or S.E-AvrA + strains. Therefore, Enteritidis AvrA-induced ZO-1 stability is achieved via suppression of the JNK pathway. Furthermore, the S.E-AvrA - strain led to enhanced bacterial invasion, both in vitro and in vivo Taken together, our data reveal a novel role for AvrA in S. Enteritidis: Enteritidis AvrA stabilizes intestinal TJs and attenuates bacterial invasion. The manipulation of JNK activity and TJs in microbial-epithelial interactions may be a novel therapeutic approach for the treatment of infectious diseases.
      (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
    • References:
      Gastroenterology. 2001 Sep;121(3):566-79. (PMID: 11522741)
      PLoS Pathog. 2012;8(7):e1002810. (PMID: 22911370)
      J Nutr. 2011 May;141(5):769-76. (PMID: 21430248)
      EMBO J. 2001 May 1;20(9):2131-9. (PMID: 11331579)
      Curr Opin Cell Biol. 1998 Apr;10(2):205-19. (PMID: 9561845)
      J Pharmacol Exp Ther. 2006 Jan;316(1):1-7. (PMID: 16002462)
      J Infect. 2007 Mar;54(3):245-9. (PMID: 16824609)
      Infect Immun. 2003 May;71(5):2839-58. (PMID: 12704158)
      Gastroenterology. 2001 Sep;121(3):580-91. (PMID: 11522742)
      Cell Host Microbe. 2008 Apr 17;3(4):233-44. (PMID: 18407067)
      Clin Infect Dis. 2010 Mar 15;50(6):882-9. (PMID: 20158401)
      Am J Physiol Cell Physiol. 2009 Sep;297(3):C775-87. (PMID: 19605737)
      Am J Pathol. 2007 Sep;171(3):882-92. (PMID: 17690189)
      FEMS Microbiol Rev. 2012 Nov;36(6):1023-45. (PMID: 22250915)
      Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):14007-12. (PMID: 22893683)
      Emerg Infect Dis. 2011 Jan;17(1):7-15. (PMID: 21192848)
      Infect Immun. 2006 Dec;74(12):6581-9. (PMID: 17015453)
      PLoS One. 2013;8(3):e58606. (PMID: 23505542)
      Am J Pathol. 2006 Nov;169(5):1686-700. (PMID: 17071592)
      Foodborne Pathog Dis. 2011 Aug;8(8):887-900. (PMID: 21492021)
      Clin Infect Dis. 2006 Aug 15;43(4):512-7. (PMID: 16838242)
      Am J Infect Control. 2006 Aug;34(6):348-50. (PMID: 16877102)
      Cases J. 2008 May 12;1(1):5. (PMID: 18577242)
      Gut. 2015 Jul;64(7):1082-94. (PMID: 25080448)
      Clin Infect Dis. 2008 Apr 1;46(7):963-9. (PMID: 18444810)
      Biochim Biophys Acta. 2008 Mar;1778(3):588-600. (PMID: 17916321)
      Cell Microbiol. 2006 Dec;8(12):1946-57. (PMID: 16869830)
      J Biol Chem. 2015 May 1;290(18):11515-25. (PMID: 25795781)
      Biochimie. 2004 Aug;86(8):533-41. (PMID: 15388230)
      J Immunol. 2002 Sep 15;169(6):2846-50. (PMID: 12218096)
      Biochem J. 2006 Jan 1;393(Pt 1):69-77. (PMID: 16134968)
      PLoS Pathog. 2009 Sep;5(9):e1000595. (PMID: 19779561)
      Am J Physiol Gastrointest Liver Physiol. 2011 Dec;301(6):G992-G1003. (PMID: 21903761)
      J Am Soc Echocardiogr. 2009 Feb;22(2):210.e1-3. (PMID: 19135858)
      Biochim Biophys Acta. 2009 Apr;1788(4):832-41. (PMID: 19059200)
      FEBS Lett. 2010 Mar 5;584(5):911-6. (PMID: 20083111)
      J Biol Chem. 2016 Feb 26;291(9):4779-92. (PMID: 26724804)
      Nat Commun. 2016 Apr 12;7:11273. (PMID: 27068492)
      J Cell Biol. 1993 Dec;123(6 Pt 2):1631-3. (PMID: 8276885)
      MMWR Morb Mortal Wkly Rep. 2007 Aug 31;56(34):877-9. (PMID: 17728692)
      Emerg Infect Dis. 2014 Jul;20(7):1097-104. (PMID: 24960614)
      J Transl Med. 2012 Mar 07;10:40. (PMID: 22397627)
      Histochem Cell Biol. 2015 May;143(5):471-9. (PMID: 25511417)
      Int J Infect Dis. 2009 Nov;13(6):e463-6. (PMID: 19269872)
      J Cell Biol. 1993 Nov;123(4):895-907. (PMID: 8227148)
      Clin Infect Dis. 2009 Aug 15;49(4):606-11. (PMID: 19591599)
      FASEB J. 2009 Nov;23(11):3874-83. (PMID: 19667122)
      J Biol Chem. 2010 Mar 19;285(12):8675-86. (PMID: 20071333)
      Am J Physiol. 1997 Oct;273(4 Pt 1):C1378-85. (PMID: 9357784)
      J Histochem Cytochem. 2001 Mar;49(3):333-40. (PMID: 11181736)
      PLoS One. 2008 Jun 04;3(6):e2369. (PMID: 18523661)
      Tissue Barriers. 2015 Apr 03;3(1-2):e972849. (PMID: 25838979)
      Tissue Barriers. 2013 Oct 1;1(4):e24894. (PMID: 24665406)
      Toxicol Appl Pharmacol. 2010 Jun 15;245(3):291-8. (PMID: 20362602)
      Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5. (PMID: 10829079)
      Cell Cycle. 2009 Jul 1;8(13):2110-21. (PMID: 19502798)
      J Cell Physiol. 2010 Nov;225(3):720-33. (PMID: 20533305)
      Physiol Rep. 2015 Apr;3(4):null. (PMID: 25847918)
      J Biol Chem. 2011 Apr 8;286(14):12123-32. (PMID: 21262973)
    • Grant Information:
      R01 DK105118 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: Salmonella enterica; c-Jun N-terminal kinase (JNK); infection; inflammation; tight junction
    • Accession Number:
      0 (AvrA protein, Salmonella enterica)
      0 (Bacterial Proteins)
      0 (Mutant Proteins)
      0 (Tjp1 protein, mouse)
      0 (Zonula Occludens-1 Protein)
      EC 2.7.12.2 (MAP Kinase Kinase 4)
    • Publication Date:
      Date Created: 20161123 Date Completed: 20170601 Latest Revision: 20210205
    • Publication Date:
      20231215
    • Accession Number:
      PMC5207190
    • Accession Number:
      10.1074/jbc.M116.757393
    • Accession Number:
      27875307