title: Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway.
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.
authors.affiliation: From the Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis and.|the Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, and.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Lin
authors.affiliation: the Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, and.
authors.forename: Yong-Guo
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: the Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, and.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Xia
authors.affiliation: From the Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis and.|the Center for Comparative Medicine, Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.|the Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, Illinois 60612.
authors.forename: Xiulong
authors.initials: X
authors.lastname: Xu
authors.affiliation: From the Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis and.
authors.forename: Xinan
authors.initials: X
authors.lastname: Jiao
authors.affiliation: From the Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis and junsun7@uic.edu.|the Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, and.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0001-7465-3133
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D012481:Salmonella Infections, Animal / Q000378:metabolism* / Q000382:microbiology; D012477:Salmonella enteritidis / Q000502:physiology*; D015398:Signal Transduction; D019108:Tight Junctions / Q000382:microbiology / Q000502:physiology*; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C495717:AvrA protein, Salmonella enterica; D001426:Bacterial Proteins; D050505:Mutant Proteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D048670:MAP Kinase Kinase 4
keywords: Salmonella enterica; c-Jun N-terminal kinase (JNK); infection; inflammation; tight junction