PMID- 20732430 OWN - NLM STAT- MEDLINE DCOM- 20110203 LR - 20101012 IS - 1095-9947 (Electronic) IS - 1050-4648 (Linking) VI - 29 IP - 6 DP - 2010 Dec TI - The iron-cofactored superoxide dismutase of Edwardsiella tarda inhibits macrophage-mediated innate immune response. PG - 972-8 LID - 10.1016/j.fsi.2010.08.004 [doi] AB - Edwardsiella tarda is a Gram-negative bacterium that can infect a wide variety of marine and freshwater fish and cause severe economic losses worldwide. With an aim to elucidate the virulence mechanism of E. tarda, we in this study cloned and analyzed the function of an iron-cofactored superoxide dismutase (FeSOD) from a pathogenic E. tarda strain TX01 isolated from diseased fish. FeSOD is 192-residue in length and contains domain structures that are conserved among iron/manganese superoxide dismutases. Recombinant FeSOD purified from Escherichia coli exhibits apparent superoxide dismutase activity. Quantitative real-time RT-PCR analysis indicated that FeSOD expression is significantly upregulated immediately following TX01 infection of Japanese flounder (Paralichthys olivaceus) head kidney (HK) macrophages and cultured FG cells. Compared to the wild type strain TX01, the FeSOD mutant strain TXSod is (i) more sensitive to H(2)O(2)-induced oxidative damage, (ii) less resistant against serum- and macrophage-mediated bacterial killing, (iii) significantly weakened in the ability to invade into FG cells and to disseminate in fish blood and liver, and (iv) deficient in blocking macrophage respiratory burst activity and production of reactive oxygen species. Furthermore, HK macrophages infected by TXSod exhibits significantly increased expression of inflammatory cytokines compared to macrophages infected by TX01. Taken together, these results indicate that FeSOD is a virulence factor that plays an important role in the pathogenicity of E. tarda by inhibiting macrophage-mediated innate immune response. CI - Copyright (c) 2010 Elsevier Ltd. All rights reserved. FAU - Cheng, Shuang AU - Cheng S AD - Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, PR China. FAU - Zhang, Min AU - Zhang M FAU - Sun, Li AU - Sun L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100821 PL - England TA - Fish Shellfish Immunol JT - Fish & shellfish immunology JID - 9505220 RN - 0 (DNA, Bacterial) RN - 0 (Recombinant Proteins) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Animals MH - Cloning, Molecular MH - DNA, Bacterial/chemistry/genetics MH - Edwardsiella tarda/*enzymology/genetics/immunology/pathogenicity MH - Enterobacteriaceae Infections/enzymology/microbiology/*veterinary MH - Fish Diseases/immunology/*microbiology MH - *Flounder MH - Immunity, Innate/immunology MH - Macrophages/*immunology MH - Mutagenesis, Site-Directed/veterinary MH - Polymerase Chain Reaction/veterinary MH - Recombinant Proteins/genetics/immunology MH - Sequence Analysis, DNA MH - Superoxide Dismutase/genetics/*immunology MH - Virulence/immunology EDAT- 2010/08/25 06:00 MHDA- 2011/02/04 06:00 CRDT- 2010/08/25 06:00 PHST- 2010/07/11 00:00 [received] PHST- 2010/08/10 00:00 [revised] PHST- 2010/08/10 00:00 [accepted] PHST- 2010/08/25 06:00 [entrez] PHST- 2010/08/25 06:00 [pubmed] PHST- 2011/02/04 06:00 [medline] AID - S1050-4648(10)00257-3 [pii] AID - 10.1016/j.fsi.2010.08.004 [doi] PST - ppublish SO - Fish Shellfish Immunol. 2010 Dec;29(6):972-8. doi: 10.1016/j.fsi.2010.08.004. Epub 2010 Aug 21.