Temperature and Mg2+ Sensing by a Novel PhoP-PhoQ Two-component System for Regulation of Virulence in Edwardsiella tarda

Chakraborty, Samarjit; Li, Mo; Chatterjee, C.; Sivaraman, J.; Leung, Ka Yin; Mok, Yu Keung

doi:10.1074/jbc.m110.179150

Cited by 75 publications

(84 citation statements)

References 45 publications

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“…1). The dependence of E. tarda PPD130/91 survival/replication in BMDMs on temperature is consistent with the role of temperature in the regulation of its T3SS (5,27,28). At 37°C, the expression and secretion of T3SS were suppressed via the downregulated expression of the two-component system regulatory protein EsrB by the PhoP-PhoQ system (28).…”

Section: Discussionsupporting

confidence: 53%

“…Replication of E. tarda PPD130/91 in fish epithelial cells and primary macrophages depends on its T3SS (3), whose expression is regulated by the ambient cultivating temperature in vitro (5,27,28). To recapitulate E. tarda replication in BMDMs and investigate the effect of temperature on this process, the E. tarda wild-type strain PPD130/91 was grown at 30°C to activate the T3SS and used to infect BMDMs at 37°C or 30°C.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

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

et al. 2014

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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: 98%

“…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).…”

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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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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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“…Expression of T3SS genes of E. tarda PPD130/91 is drastically downregulated when the bacteria are growing at 37°C; therefore, we performed infections at 35°C, conditions under which the T3SS genes are well expressed (18,32). J774A.1 macrophages were incubated with the wild-type or ⌬eseJ mutant strain for 30 min at 35°C and then washed extensively before cells were lysed for plating (T0) or for infection for either another 30 min (T0.5) or 1 h (T1) in DMEM containing 100 g/ml gentamicin followed by bacterial enumeration.…”

Section: Fig 4 Esej Inhibits E Tarda Adhesion To Epc Cells From Insimentioning

confidence: 99%

Identification and Functional Characterization of the Novel Edwardsiella tarda Effector EseJ

et al. 2015

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e Edwardsiella tarda is a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish and gastro-and extraintestinal infections in humans. The type III secretion system (T3SS) of E. tarda has been identified as a key virulence factor that contributes to pathogenesis in fish. However, little is known about the associated effectors translocated by this T3SS. In this study, by comparing the profile of secreted proteins of the wild-type PPD130/91 and its T3SS ATPase ⌬esaN mutant, we identified a new effector by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. This effector consists of 1,359 amino acids, sharing high sequence similarity with Orf29/30 of E. tarda strain EIB202, and is renamed EseJ. The secretion and translocation of EseJ depend on the T3SS. A ⌬eseJ mutant strain adheres to epithelioma papillosum of carp (EPC) cells 3 to 5 times more extensively than the wild-type strain does. EseJ inhibits bacterial adhesion to EPC cells from within bacterial cells. Importantly, the ⌬eseJ mutant strain does not replicate efficiently in EPC cells and fails to replicate in J774A.1 macrophages. In infected J774A.1 macrophages, the ⌬eseJ mutant elicits higher production of reactive oxygen species than wild-type E. tarda. The replication defect is consistent with the attenuation of the ⌬eseJ mutant in the blue gourami fish model: the 50% lethal dose (LD 50 ) of the ⌬eseJ mutant is 2.34 times greater than that of the wild type, and the ⌬eseJ mutant is less competitive than the wild type in mixed infection. Thus, EseJ represents a novel effector that contributes to virulence by reducing bacterial adhesion to EPC cells and facilitating intracellular bacterial replication.

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Temperature and Mg2+ Sensing by a Novel PhoP-PhoQ Two-component System for Regulation of Virulence in Edwardsiella tarda

Cited by 75 publications

References 45 publications

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

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

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

Identification and Functional Characterization of the Novel Edwardsiella tarda Effector EseJ

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