title: Edwardsiella tarda-Induced cytotoxicity depends on its type III secretion system and flagellin.
abstract: Many Gram-negative bacteria utilize a type III secretion system (T3SS) to translocate virulence proteins into host cells to cause diseases. In responding to infection, macrophages detect some of the translocated proteins to activate caspase-1-mediated cell death, called pyroptosis, and secretion of proinflammatory cytokines to control the infection. Edwardsiella tarda is a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish and both gastrointestinal and extraintestinal infections in humans. In this study, we report that the T3SS of E. tarda facilitates its survival and replication in murine bone marrow-derived macrophages, and E. tarda infection triggers pyroptosis of infected macrophages from mice and fish and increased secretion of the cytokine interleukin 1β in a T3SS-dependent manner. Deletion of the flagellin gene fliC of E. tarda results in decreased cytotoxicity for infected macrophages and does not attenuate its virulence in a fish model of infection, whereas upregulated expression of FliC in the fliC mutant strain reduces its virulence. We propose that the host controls E. tarda infection partially by detecting FliC translocated by the T3SS, whereas the bacteria downregulate the expression of FliC to evade innate immunity.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Lu
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rolhion
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Holden
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China pinnie@ihb.ac.cn x.yu@imperial.ac.uk.
authors.forename: Pin
authors.initials: P
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom pinnie@ihb.ac.cn x.yu@imperial.ac.uk.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis; D058947:Bacterial Secretion Systems; D002470:Cell Survival; D020609:Edwardsiella tarda / Q000378:metabolism* / Q000472:pathogenicity; D005399:Fishes; D005408:Flagellin / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D058947:Bacterial Secretion Systems; D053583:Interleukin-1beta; D037521:Virulence Factors; D005408:Flagellin