Identification and Characterization of Putative Translocated Effector Proteins of the Edwardsiella ictaluri Type III Secretion System

Dubytska, Lidiya; Rogge, Matthew L.; Thune, Ronald L.

doi:10.1128/msphere.00039-16

Cited by 19 publications

(33 citation statements)

References 58 publications

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“…Closely related to E. tarda, Edwardsiella ictaluri is another fish pathogen that multiplies within the Edwardsiella ictaluri-containing vacuole (EiCV). The EiCV demonstrates an initial acidification and subsequent neutralization, which leads to the translocation of effectors into the host cytosol (37)(38)(39). Although it remains to be determined if EtCVs and EiCVs display similar pH dynamics during their maturation, we believe that the EsaB/EsaL/EsaM complex ensured proper function of the T3SS at acidic pH and is ideal for E. tarda to adapt to its intracellular life.…”

Section: Discussionmentioning

confidence: 94%

“…However, this complex dissociates at neutral pH, triggering the secretion of effectors but not translocon proteins. Similar to Salmonella, Edwardsiella ictaluri, a fish pathogen that shares a common virulence strategy with E. tarda (35)(36)(37), resides in E. ictaluri-containing vacuoles (EiCVs) that undergo an initial acidification and subsequent neutralization, ultimately leading to the translocation of effectors into the host cytosol (37)(38)(39). We hypothesized that a pH shift might also trigger the secretion of effectors by the E. tarda T3SS.…”

Section: Figmentioning

confidence: 99%

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Regulation of Type III Secretion of Translocon and Effector Proteins by the EsaB/EsaL/EsaM Complex in Edwardsiella tarda

Liu

Nie

et al. 2017

Infect Immun

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The type III secretion system (T3SS) plays a crucial role in the pathogenesis of many Gram-negative bacteria, including , an important fish pathogen. Within the T3SS, there are three proteins (EsaB/EsaL/EsaM) that are homologous to proteins present in many other bacteria, including SpiC/SsaL/SsaM in , SepD/SepL/CesL in enteropathogenic (EPEC) and enterohemorrhagic (EHEC), and YscB/YopN/SycN in EsaL was found to interact with both EsaB and EsaM within the bacterial cell, as revealed by a coimmunoprecipitation assay. Moreover, EsaM is required for EsaB stability, and the two proteins interact with each other. EsaB, EsaL, and EsaM are all indispensable for the secretion of the T3SS translocon protein EseC into supernatants under pH 5.5 and pH 7.2 conditions. Unlike EseC, EseG is a T3SS effector whose secretion is suppressed by EsaL at pH 7.2 while it is promoted at pH 5.5 condition. Despite this finding, mutant strains lacking EsaB, EsaL, or EsaM (i.e., the Δ, Δ, or Δ strain, respectively) were all outcompeted by wild-type during a coinfection model. These results demonstrate that EsaB/EsaL/EsaM form a ternary complex controlling the secretion of T3SS translocon and effector proteins and contributing to pathogenesis.

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Section: Discussionmentioning

confidence: 94%

Section: Figmentioning

confidence: 99%

Regulation of Type III Secretion of Translocon and Effector Proteins by the EsaB/EsaL/EsaM Complex in Edwardsiella tarda

Liu

Nie

et al. 2017

Infect Immun

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“…It has been shown that E. ictaluri Type III Secretion System (T3SS) is tightly regulated and expressed inside the catfish macrophages (Rogge & Thune, 2011). The T3SS effector proteins secreted into macrophages manipulate the pathways of host cells (Dubytska, Rogge, & Thune, 2016;Zhao et al, 2013), and deletion of them impairs the intracellular replication of E. ictaluri (Thune et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Edwardsiella ictaluri evpP is required for colonisation of channel catfish ovary cells and necrosis in anterior kidney macrophages

Kalindamar

Kordon

Abdelhamed

et al. 2019

Cellular Microbiology

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Edwardsiella ictaluri is a Gram-negative facultative anaerobe that can survive inside channel catfish phagocytes. E. ictaluri can orchestrate Type VI Secretion System (T6SS) for survival in catfish macrophages. evpP encodes one of the T6SS translocated effector proteins. However, the role of evpP in E. ictaluri is still unexplored. In this work, we constructed an E. ictaluri evpP mutant (EiΔevpP) and assessed its survival under complement and oxidative stress. Persistence of EiΔevpP in catfish as well as attachment and invasion in catfish macrophage and ovary cells were determined. Further, virulence of EiΔevpP in catfish and apoptosis it caused in macrophages were explored. EiΔevpP behaved same as wild type (EiWT) under complement and oxidative stress in complex media, whereas oxidative stress affected mutant's survival significantly in minimal media (p < .05). Persistence of EiΔevpP in live catfish and uptake and survival inside peritoneal macrophages were similar. The attachment and invasion capabilities of EiΔevpP in catfish ovary cells were significantly less than that of EiWT (p < .05). Although EiΔevpP showed reduced attenuation in catfish, causing decreased catfish mortality compared with EiWT (44.73% vs. 67.53%), this difference was not significant. The apoptosis assay using anterior kidney macrophages indicated that the number of live macrophages exposed to EiΔevpP was significantly higher compared with EiWT exposed macrophages at 24-hr post-treatment (p < .05). However, there were no significant differences in the early and late apoptosis. Remarkably, necrosis in EiΔevpP exposed macrophages was significantly less than that of EiWT exposed macrophages at 24 hr (p < .05). Our results demonstrated that evpP is required for colonisation of catfish ovary cells and increased apoptosis and necrosis in anterior kidney macrophages.

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“…All 9 putative effectors appeared to be absent from the genomes of E. hoshinae ATCC33379 and E. tarda ATCC15947 (Tables 1 and S2). Furthermore, of the reported list of 9 effectors in E. ictaluri, only EseG and EseN are shared by E. piscicida, and the remaining 7 effectors are absent in all the other species, 55 suggesting a specific basis for the evolution of pathogenic mechanisms and host specificity in the evolutionary history of these Edwardsiella species.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Dubytska et al identified 9 putative T3SS effectors using bioinformatics and a cyaAbased translocation assay. 55 Of these 9 effectors, 5 contain leucine-rich repeat protein (LRR) domains with various numbers of repeats. Interestingly, stringent BLASTP analysis indicated that, among the 9 effectors identified here, ETAE_3282 is not found in the published E. ictaluri genomes.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic dissection of the horizontally acquired response regulator EsrB reveals its global regulatory roles in the physiological adaptation and activation of T3SS and the cognate effector repertoire inEdwardsiella piscicidaduring infection toward turbot

et al. 2017

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(2017) Transcriptomic dissection of the horizontally acquired response regulator EsrB reveals its global regulatory roles in the physiological adaptation and activation of T3SS and the cognate effector repertoire in Edwardsiella piscicida during infection toward turbot, Virulence, 8:7, 1355-1377, DOI: 10.1080/21505594.2017 ABSTRACTEdwardsiella piscicida is the leading pathogen threatening worldwide aquaculture industries. The 2-component system (TCS) EsrA-EsrB is essential for the pathogenesis of this bacterium. However, little is known about the regulon and regulatory mechanism of EsrA-EsrB or about the factors that mediate the interaction of TCS with bacterial hosts. Here, our RNA-seq analysis indicated that EsrB strongly induces type III and type VI secretion systems (T3/T6SS) expression and that it modulates the expression of both physiology-and virulence-associated genes in E. piscicida grown in DMEM. EsrB binds directly to a highly conserved 18-bp DNA motif to regulate the expression of T3SS and other genes. EsrB/DMEM-activated genes include 3 known and 6 novel T3SS-dependent effectors. All these effector genes are highly induced by EsrB during the late stage of in vivo infection in fish. Furthermore, although in vivo colonization by the bacterium relies on EsrB and T3/T6SS expression, it does not require the expression of individual effectors other than EseJ. The mutant lacking these 9 effectors showed significant defects in in vivo colonization and virulence toward turbot, and, more importantly, a high level of protection against challenges by wild-type E. piscicida, suggesting that it may represent a promising live attenuated vaccine. Taken together, our data demonstrate that EsrB plays a global regulatory role in controlling physiologic responses and the expression of T3SS and its cognate effector genes. Our findings will facilitate further work on the mechanism of molecular pathogenesis of this bacterium during infection.

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Identification and Characterization of Putative Translocated Effector Proteins of the Edwardsiella ictaluri Type III Secretion System

Cited by 19 publications

References 58 publications

Regulation of Type III Secretion of Translocon and Effector Proteins by the EsaB/EsaL/EsaM Complex in Edwardsiella tarda

Regulation of Type III Secretion of Translocon and Effector Proteins by the EsaB/EsaL/EsaM Complex in Edwardsiella tarda

Edwardsiella ictaluri evpP is required for colonisation of channel catfish ovary cells and necrosis in anterior kidney macrophages

Transcriptomic dissection of the horizontally acquired response regulator EsrB reveals its global regulatory roles in the physiological adaptation and activation of T3SS and the cognate effector repertoire inEdwardsiella piscicidaduring infection toward turbot

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