The type III secretion system-dependent repression of NF-κB activation to the intracellular growth of Edwardsiella tarda in human epithelial cells

Okuda, Jun; Kiriyama, Makoto; Yamanoi, Eisuke; Nakai, Toshiko

doi:10.1111/j.1574-6968.2008.01147.x

Cited by 22 publications

(14 citation statements)

References 14 publications

(22 reference statements)

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“…E. tarda prefers an intracellular lifestyle during infection in either epithelial (21,22) or phagocytic (15,23,24) cells, which provide an intracellular niche for this pathogen. In this study, we established an E. tarda infection model in murine macrophage-like cell line J774A.1.…”

Section: Resultsmentioning

confidence: 99%

Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda

Zhang

et al. 2016

J Bacteriol

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Edwardsiella tarda is an important pathogenic bacterium that can replicate in macrophages. However, how the intramacrophage infection process affects the virulence of this bacterium is essentially unknown. Here, we show that E. tarda replicates and induces a caspase-1-dependent cell pyroptosis in a murine macrophage model. Via pyroptosis, intracellular E. tarda escapes to the extracellular milieu, forming a unique bacterial population. Being different from the bacteria cultured alone, this unique population possesses a reprogrammed transcriptional profile, particularly with upregulated type III secretion system (T3SS)/T6SS cluster genes. Subsequent studies revealed that the macrophage-released population gains enhanced infectivity for host epithelial cells and increases resistance to multiple host defenses and hence displays significantly promoted virulence in vivo. Further studies indicated that T3SS is essentially required for the macrophage infection process, while T6SS contributes to infection-induced bacterial virulence. Altogether, this work demonstrates that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, suggesting a positive role for intramacrophage infection in bacterial pathogenesis. IMPORTANCEMany pathogens can replicate in macrophages, which is crucial for their pathogenesis. To survive in the macrophage cell, pathogens are likely to require fitness genes to counteract multiple host-killing mechanisms. Here, Edwardsiella tarda is proved to exit from macrophages during infection. This macrophage-released population displays a reprogrammed transcriptional profile with significantly upregulated type III secretion system (T3SS)/T6SS-related genes. Furthermore, both enhanced infectivity in epithelial cells and activated resistance to complex host defenses were conferred on this macrophage-primed population, which consequently promoted the full virulence of E. tarda in vivo. Our work provides evidence that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, highlighting the importance of the intramacrophage infection cycle for the pathogenesis of E. tarda.

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Section: Resultsmentioning

confidence: 99%

Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda

Zhang

et al. 2016

J Bacteriol

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“…For example, when one of the two T3SS-regulatory genes, esrB and esrC, was deleted in E. tarda PPD130/91, the LD 50 s of the resulting mutants were 3 log units higher than that of the wild type (43,56). Although it has been speculated that Edwardsiella effectors may be responsible for the intracellular growth of the bacteria in HEp-2 cells (34) and for their multiplication in murine and fish macrophages (33,45), no T3SS effectors of E. tarda have been identified yet. In this study, we have identified the first effector of E. tarda, EseG.…”

Section: Discussionmentioning

confidence: 99%

“…The T3SS facilitates the survival of E. tarda in phagocytes and HEp-2 cells (19,33,34,45) and contributes to virulence in vivo (45). The deletion of various single T3SS genes, such as escC, eseB, eseD, or escA, increased the 50% lethal dose (LD 50 ) by approximately 1 log unit in blue gourami (49,55).…”

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confidence: 99%

EseG, an Effector of the Type III Secretion System of Edwardsiella tarda , Triggers Microtubule Destabilization

Xie

Zheng

et al. 2010

Infect Immun

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Edwardsiella tarda is a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish and both gastrointestinal and extraintestinal infections in humans. A type III secretion system (T3SS) was recently shown to contribute to pathogenesis, since deletions of various T3SS genes increased the 50% lethal dose (LD 50 ) by about 1 log unit in the blue gourami infection model. In this study, we report EseG as the first identified effector protein of T3SS. EseG shares partial homology with two Salmonella T3SS effectors (SseG and SseF) over a conserved domain (amino acid residues 142 to 192). The secretion of EseG is dependent on a functional T3SS and, in particular, requires the chaperone EscB. Experiments using TEM-1 ␤-lactamase as a fluorescence-based reporter showed that EseG was translocated into HeLa cells at 35°C. (EseG 142-192 ), since truncated versions of EseG devoid of this motif lose their ability to cause microtubule destabilization. By demonstrating the function of EseG, our study contributes to the understanding of E. tarda pathogenesis. Moreover, the approach established in this study to identify type III effectors can be used to identify and characterize more type III and possible type VI effectors in Edwardsiella. Fractionation of infected HeLa cells demonstrated that EseG was localized to the host membrane fraction after translocation. EseG is able to disassemble microtubule structures when overexpressed in mammalian cells. This phenotype may require a conserved motif of EseG

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“…Deletion of its T3SS ATPase gene esaN increased the 50% lethal dose (LD 50 ) by approximately 1 log in the blue gourami infection model (5). The T3SS facilitates the survival and replication of different E. tarda isolates in different eukaryotic cells, such as Hep-2 epithelial cells (6), the epithelioma papillosum of carp cells (3), J774A.1 macrophages (4), and fish primary macrophages (3,7).…”

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confidence: 99%

Edwardsiella tarda-Induced Cytotoxicity Depends on Its Type III Secretion System and Flagellin

et al. 2014

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bMany 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 1␤ 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.

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The type III secretion system-dependent repression of NF-κB activation to the intracellular growth of Edwardsiella tarda in human epithelial cells

Cited by 22 publications

References 14 publications

Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda

Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda

EseG, an Effector of the Type III Secretion System of Edwardsiella tarda , Triggers Microtubule Destabilization

Edwardsiella tarda-Induced Cytotoxicity Depends on Its Type III Secretion System and Flagellin

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