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

Kalindamar, Şafak; Kordon, Adef O.; Abdelhamed, Hossam; Wang, Tan; Pinchuk, Lesya M.; Karsi, Attila

doi:10.1111/cmi.13135

Cited by 13 publications

(12 citation statements)

References 57 publications

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“…Nevertheless, in present study, it is noteworthy that more early apoptosis could be observed than late apoptosis in E. piscicida-infected macrophages, implying that cell death by apoptosis might play a significant role in E. piscicida-macrophage interactions. Although EvpP have been demonstrated to exert inhibitory effect on apoptosis and pyroptosis in E. piscicida-infected macrophages, for E. ictalurid, EvpP were shown to increase apoptosis and necrosis in anterior kidney macrophages (Kalindamar et al, 2019). Additionally, in contrast to E. piscicida, deletion of evpP were not found to affect the virulence of E. ictalurid significantly in that study.…”

Section: Discussioncontrasting

confidence: 60%

“…A recent study revealed the role of EvpP in promoting the pathogenesis of E. piscicida via inhibiting the phosphorylation of Jnk signaling, subsequently suppressing the caspy-inflammasome signaling cascades, contributing to the inhibition of neutrophils recruitment (Tan et al, 2019). In E. ictalurid, EvpP were demonstrated to be required for colonization of catfish ovary cell and increase apoptosis and necrosis in anterior kidney macrophages (Kalindamar et al, 2019). These reports increasingly reveal the importance of EvpP in E. piscicida-infection.…”

Section: Introductionmentioning

confidence: 98%

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Roles of EvpP in Edwardsiella piscicida-Macrophage Interactions

Qin¹,

Wang²,

Gao³

et al. 2020

Front. Cell. Infect. Microbiol.

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Edwardsiella piscicida is found to be an important facultative intracellular pathogen with a broad host range. These organisms can replicate and survive within host macrophages to escape from the subversion of the immune defense. E. piscicida-macrophage interaction is very important in determining the outcome of edwardsiellasis. As an effector protein of E. piscicida T6SS, EvpP has been determined to be a very important virulence factor for E. piscicida, although its precise role in E. piscicida-macrophage interactions is not yet clear. In this study, the roles of EvpP in E. piscicida-macrophage interactions were characterized. Here, we constructed the deletion mutants of evpP (evpP) and complementation (evpP-C) by the allelic exchange method. Compared to wild type strain (WT), evpP was found to be attenuated for growth within macrophages. In line with this observation, we found its survival capacity was lower than WT under oxidative and acid stress in vitro, which simulate conditions encountered in host macrophages. Attenuation of evpP also correlated with enhanced activation of macrophages, as reflected by augmented NO production in evpP-treated macrophages. Moreover, compared to WT, evpP induced markedly increased apoptosis of macrophages, characterized by increased Annexin V binding and the activation of cleaved caspase-3. These findings provided strong evidence that EvpP is involved in the process of E. piscicida-macrophage interactions and is required for its survival and replication in macrophages. Thus, we propose that EvpP might be an important factor that controlling the fate of E. piscicida inside macrophages. To further exploring the underlying mechanism of EvpP action, the cDNA library was constructed from E. piscicida-infected macrophages and a yeast two-hybrid screen was performed to search for cellular proteins interacting with EvpP. Ribosomal protein S5 (RPS5) was identified as a target of EvpP. Furthermore, the interaction was validated with co-immunoprecipitation assay. This result implies that the observed effect of EvpP on macrophages might be related to RPS5-mediated regulation, contributing to a better understanding of the mechanisms of EvpP involved in E. piscicida-macrophage interactions.

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Section: Discussioncontrasting

confidence: 60%

Section: Introductionmentioning

confidence: 98%

Roles of EvpP in Edwardsiella piscicida-Macrophage Interactions

Qin¹,

Wang²,

Gao³

et al. 2020

Front. Cell. Infect. Microbiol.

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“…T6SS effectors are involved in bacterial survival in oxidative stress ( 54 , 55 ). In E. ictaluri and E. piscicida , the T6SS effector EvpP enhanced resistance to oxidative stress ( 56 , 57 ). To investigate the role of Hcp family proteins of T6SS in E. ictaluri stress resistance, we applied nitrosative and oxidative stress with SNP and H 2 O 2 in BHI and in MM19-P to imitate stressful phagosome conditions.…”

Section: Discussionmentioning

confidence: 99%

Hemolysin Co-regulated Family Proteins Hcp1 and Hcp2 Contribute to Edwardsiella ictaluri Pathogenesis

et al. 2021

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Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia of catfish (ESC), a devastating disease resulting in significant economic losses in the U.S. catfish industry. Bacterial secretion systems are involved in many bacteria's virulence, and Type VI Secretion System (T6SS) is a critical apparatus utilized by several pathogenic Gram-negative bacteria. E. ictaluri strain 93–146 genome has a complete T6SS operon with 16 genes, but the roles of these genes are still not explored. In this research, we aimed to understand the roles of two hemolysin co-regulated family proteins, Hcp1 (EvpC) and Hcp2. To achieve this goal, single and double E. ictaluri mutants (EiΔevpC, EiΔhcp2, and EiΔevpCΔhcp2) were generated and characterized. Catfish peritoneal macrophages were able to kill EiΔhcp2 better than EiΔevpC, EiΔevpCΔhcp2, and E. ictaluri wild-type (EiWT). The attachment of EiΔhcp2 and EiΔevpCΔhcp2 to ovary cells significantly decreased compared to EiWT whereas the cell invasion rates of these mutants were the same as that of EiWT. Mutants exposed to normal catfish serum in vitro showed serum resistance. The fish challenges demonstrated that EiΔevpC and EiΔevpCΔhcp2 were attenuated completely and provided excellent protection against EiWT infection in catfish fingerlings. Interestingly, EiΔhcp2 caused higher mortality than that of EiWT in catfish fingerlings, and severe clinical signs were observed. Although fry were more susceptible to vaccination with EiΔevpC and EiΔevpCΔhcp2, their attenuation and protection were significantly higher compared to EiWT and sham groups, respectively. Taken together, our data indicated that evpC (hcp1) is involved in E. ictaluri virulence in catfish while hcp2 is involved in adhesion to epithelial cells and survival inside catfish macrophages.

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“…Promotes adhesion and internalization. Kalindamar et al, 2020 (Continued) Three T6SS effectors with putative anti-eukaryotic activities were identified by analyzing the Vpr secretome. Vpr01570 contains an N-terminal MIX V domain and a C-terminal CNF1 (cytotoxic necrotizing factor 1) deamidase domain that targets and activates Rho GTPases.…”

Section: E Tarda Evppmentioning

confidence: 99%

“…EvpP toxin is involved in adhesion and internalization of E. ictaluri in catfish ovary cells. EvpP plays a role in growth regulation in the phagolysosome where oxidative stress and limited nutrients are present, and also favors survival and increases apoptosis and necrosis in catfish anterior kidney macrophages (Kalindamar et al, 2020).…”

Section: Edwardsiellamentioning

confidence: 99%

An Overview of Anti-Eukaryotic T6SS Effectors

Feria

Valvano

2020

Front. Cell. Infect. Microbiol.

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The type VI secretion system (T6SS) is a transmembrane multiprotein nanomachine employed by many Gram-negative bacterial species to translocate, in a contact-dependent manner, effector proteins into adjacent prokaryotic or eukaryotic cells. Typically, the T6SS gene cluster encodes at least 13 conserved core components for the apparatus assembly and other less conserved accessory proteins and effectors. It functions as a contractile tail machine comprising a TssB/C sheath and an expelled puncturing device consisting of an Hcp tube topped by a spike complex of VgrG and PAAR proteins. Contraction of the sheath propels the tube out of the bacterial cell into a target cell and leads to the injection of toxic proteins. Different bacteria use the T6SS for specific roles according to the niche and versatility of the organism. Effectors are present both as cargo (by non-covalent interactions with one of the core components) or specialized domains (fused to structural components). Although several anti-prokaryotic effectors T6SSs have been studied, recent studies have led to a substantial increase in the number of characterized anti-eukaryotic effectors. Against eukaryotic cells, the T6SS is involved in modifying and manipulating diverse cellular processes that allows bacteria to colonize, survive and disseminate, including adhesion modification, stimulating internalization, cytoskeletal rearrangements and evasion of host innate immune responses.

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

Cited by 13 publications

References 57 publications

Roles of EvpP in Edwardsiella piscicida-Macrophage Interactions

Roles of EvpP in Edwardsiella piscicida-Macrophage Interactions

Hemolysin Co-regulated Family Proteins Hcp1 and Hcp2 Contribute to Edwardsiella ictaluri Pathogenesis

An Overview of Anti-Eukaryotic T6SS Effectors

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