Intracellular replication of Edwardsiella tarda in murine macrophage is dependent on the type III secretion system and induces an up-regulation of anti-apoptotic NF-κB target genes protecting the macrophage from staurosporine-induced apoptosis

Okuda, Jun; Arikawa, Yoko; Takeuchi, Yukiko; Mahmoud, Mahmoud Mostafa; Suzaki, Etsuko; Kataoka, Kazunori; Suzuki, Toshiharu; Okinaka, Yasushi; Nakai, Toshiko

doi:10.1016/j.micpath.2006.08.002

Cited by 70 publications

(72 citation statements)

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“…E. tarda strain PPD130/91 was recently recognized as Edwardsiella piscicida (20,21). However, unlike the new name E. piscicida, which is not yet widely recognized, the name E. tarda PPD130/91 is well recognized from many studies, including ours (6)(7)(8)(9)(10)(11)(12)(13)(14). We thus keep the name E. tarda PPD130/91 in our current study.…”

Section: Methodsmentioning

confidence: 97%

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EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of the escC - eseE Operon

et al. 2016

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Edwardsiella tarda is an important Gram-negative pathogen that employs a type III secretion system (T3SS) to deliver effectors into host cells to facilitate bacterial survival and replication. These effectors are translocated into host cells through a translocon complex composed of three secreted proteins, namely, EseB, EseC, and EseD. The secretion of EseB and EseD requires a chaperone protein called EscC, whereas the secretion of EseC requires the chaperone EscA. In this study, we identified a novel protein (EseE) that also regulates the secretion of EseC. An eseE deletion mutant secreted much less EseC into supernatants, accompanied by increased EseC levels within bacterial cells. We also demonstrated that EseE interacted directly with EseC in a pulldown assay. Interestingly, EseC, EseE, and EscA were able to form a ternary complex, as revealed by pulldown and gel filtration assays. Of particular importance, the deletion of eseE resulted in decreased levels of EseB and EseD proteins in both the bacterial pellet and supernatant fraction. Furthermore, real-time PCR assays showed that EseE positively regulated the transcription of the translocon operon escC-eseE, comprising escC, eseB, escA, eseC, eseD, and eseE. These effects of EseE on the translocon components/operon appeared to have a functional consequence, since the ⌬eseE strain was outcompeted by wild-type E. tarda in a mixed infection in blue gourami fish. Collectively, our results demonstrate that EseE not only functions as a chaperone for EseC but also acts as a positive regulator controlling the expression of the translocon operon escC-eseE, thus contributing to the pathogenesis of E. tarda in fish.T he type III secretion system (T3SS) is a contact-dependent translocation system. It forms a syringe-like structure spanning the inner and outer membranes of bacteria and induces pore formation on host cells (1). Through these pores, an array of bacterial proteins (effectors) are delivered into host cells, where they manipulate host cell signaling pathways to promote bacterial survival (2).Edwardsiella tarda is a Gram-negative intracellular pathogen that can cause hemorrhagic septicemia in fish (3), as well as gastroand extraintestinal infections in humans (4, 5). The T3SS is well known to be one of the most important virulence factors in E. tarda (6, 7). It facilitates the survival and replication of E. tarda in host cells (6-9). E. tarda T3SS contains 34 open reading frames (ORFs), which encode the apparatus, chaperones, effectors, and regulators (6, 10). The expression of E. tarda T3SS is controlled by many factors, such as the two-component system esrA-esrB (6) and esrC (11) inside the T3SS gene cluster, as well as phoP-phoQ (12) and phoR-phoB (13) located outside the T3SS gene cluster. Intriguingly, our group recently showed that a type III secretion system-secreted protein (EscE) also functions as a regulator controlling the injection of effectors and secretion of translocators (14).EseB, EseC, and EseD, secreted by the E. tarda T3SS, are homologous ...

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Section: Methodsmentioning

confidence: 97%

“…The T3SS is well known to be one of the most important virulence factors in E. tarda (6,7). It facilitates the survival and replication of E. tarda in host cells (6)(7)(8)(9). E. tarda T3SS contains 34 open reading frames (ORFs), which encode the apparatus, chaperones, effectors, and regulators (6,10).…”

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confidence: 99%

EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of the escC - eseE Operon

et al. 2016

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“…Dis Aquat Org 84: [115][116][117][118][119][120][121] 2009 macrophages is important for efficient intracellular growth of bacteria in the macrophages (Okuda et al 2006). However, only scant information is available on the pathogenicity of E. tarda.…”

Section: Resale or Republication Not Permitted Without Written Consenmentioning

confidence: 99%

“…Among these virulence factors, the ability to resist phagocyte-mediated killing by failing to trigger the respiratory burst gives it a niche advantage in the host (Srinivasa Rao et al 2001). In addition, we have recently reported that the anti-apoptotic effect of its infection in murine macrophages is important for efficient intracellular growth of bacteria in the macrophages (Okuda et al 2006). However, only scant information is available on the pathogenicity of E. tarda.…”

Section: Introductionmentioning

confidence: 99%

Characterization of proteins secreted from a Type III secretion system of Edwardsiella tarda and their roles in macrophage infection

Okuda¹,

Kiriyama²,

Suzaki³

et al. 2009

Dis. Aquat. Org.

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The Type III secretion system is essential for intracellular replication of Edwardsiella tarda in phagocytes of fish and mammals. We identified the secreted proteins of the Type III secretion system by comparing the wild-type strain and the Type III mutant mET1229. The wild-type strain secreted 55, 25, and 22 kDa proteins into the culture supernatant, whereas the Type III mutant did not. These proteins were identified as EseB, EseC, and EseD and are similar in sequence to Salmonella SseB, SseC, and SseD that function as a translocon. The EseB, EseC, and EseD knockout mutants did not replicate in murine macrophages, suggesting that these proteins are essential for intracellular replication of E. tarda. Highest secretion of EseBCD proteins was observed when bacterial cells were cultured in neutral and alkaline pHs but not in acidic pH. When the pH of the phagosomes was examined using an acidotropic probe, the phagosomes containing the wild-type strain showed neutral pH, whereas those containing the Type III mutant exhibited acidic pH. These results suggest that the Type III-dependent interference with formation of the acidic environment in phagosomes is essential for intracellular replication of bacteria in murine macrophages. KEY WORDS: Edwardsiella tarda · EseBCD proteins · Translocon · Phagosomal pH · Macrophage Resale or republication not permitted without written consent of the publisherDis Aquat Org 84: [115][116][117][118][119][120][121] 2009 macrophages is important for efficient intracellular growth of bacteria in the macrophages (Okuda et al. 2006). However, only scant information is available on the pathogenicity of E. tarda.Many gram-negative pathogenic bacteria use a conserved protein secretion machinery termed 'Type III secretion system' (TTSS) to transport virulence factors and cause disease. The TTSS apparatus consists of approximately 20 to 25 proteins. The unique feature of the TTSS is a needle-like structure through which particular proteins (termed 'effectors') are injected into host cells. Effectors play an important role in the pathogenic relationship between host and bacterium. Injection of effectors into host cells occurs through pores (termed 'translocons)' formed in the host cell membrane by the TTSS using Type III-secreted proteins (Ghosh 2004). The TTSS encoded within Salmonella pathogenicity island 2 (SPI2) is essential for its intracellular accumulation in macrophages. SseB, SseC, and SseD proteins secreted from the TTSS encoded within SPI2 are reported to function as translocons (Nikolaus et al. 2001). Using TnphoA transposon tagging and the proteomics approach, a TTSS was found in Edwardsiella tarda that was similar to that encoded within SPI2 of Salmonella (Srinivasa Rao et al. 2003, Tan et al. 2005. Three TTSS proteins of E. tarda, homologous to SseBCD were identified and these proteins were designated as EseB, EseC, and EseD (Srinivasa Rao et al. 2004, Tan et al. 2005. We reported that, similar to Salmonella, the TTSS encoded within E. tarda is required for its intra...

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“…The virulence of E. tarda strains is associated with multiple factors including siderophores and hemolysins (Hirono et al, 1997), motility conferred by the flagellum (Mathew et al, 2001), and a type three secretion system (TTSS) that confers survival and replication advantages within macrophages (Rao et al, 2004;Zheng et al, 2005;Okuda et al, 2006). E. tarda as a typical facultative intracellular pathogen resists reactive oxygen species (ROS) and survives within phagocytic cells (Ishibe et al, 2008), a feature that is partially due to the production of enzymes including an iron-cofactored superoxide dismutase (FeSOD) (Cheng et al, 2010), and heat shock proteins (Dang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Nuevos genes relacionados con el sistema secretor tipo 4 de Edwardsiella tarda

2015

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SummaryEdwardsiella tarda is a Gram-negative bacterium that causes edwardsiellosis, a disease of fish and mammals including humans and characterized by multiple abscesses. Different strains of E. tarda possess a number of virulence, antibioticresistance, and toxin secretion system-related genes that explain in some extent its capacity to survive within phagocytic cells and to infect a variety of hosts. Previously we introduced a virulent E. tarda strain (ETSJ54) isolated from Japanese flounder (Paralichthys olivaceus) with edwardsiellosis and reported a number of virulence-related genes. In this study we have re-analyzed the sequencing data of ETSJ54 and identified novel type IV secretion system-related genes, most of them were flanked by transposase and plasmid encoding genes. Interestingly, their nucleotide sequence had no identity to those of the genes published in the E. tarda EIB202 genome, a virulent strain isolated from turbot (Scophthalmus maximus) in China. The results suggest differences in gene content between geographically distinct E. tarda strains that may encourage additional E. tarda genome sequencing projects.

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Intracellular replication of Edwardsiella tarda in murine macrophage is dependent on the type III secretion system and induces an up-regulation of anti-apoptotic NF-κB target genes protecting the macrophage from staurosporine-induced apoptosis

Cited by 70 publications

References 87 publications

EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of the escC - eseE Operon

EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of the escC - eseE Operon

Characterization of proteins secreted from a Type III secretion system of Edwardsiella tarda and their roles in macrophage infection

Nuevos genes relacionados con el sistema secretor tipo 4 de Edwardsiella tarda

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