Dysregulated haemolysin promotes bacterial outer membrane vesicles-induced pyroptotic-like cell death in zebrafish

Wen, Ying; Chen, Shouwen; Jiang, Zhiwei; Wang, Zhuang; Tan, Jinchao; Hu, Tianjian; Wang, Qiyao; Zhou, Xiangshan; Zhang, Yuanxing; Liu, Qin; Yang, Dahai

doi:10.1111/cmi.13010

Cited by 11 publications

(10 citation statements)

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“…As described previously, a qualitative method based on cellular morphological observation and a quantitative method detecting the release cytosolic contents were used to examine cell death, respectively (Wen et al, 2019). Cells were treated as described previously in 24-well plates and the dynamic morphological changes of cells were captured using an Olympus IX71 fluorescent microscope at room temperature.…”

Section: Cell Death Assaymentioning

confidence: 99%

“…To explore the physiologic function of cell death and the strategies used by pathogens to regulate host cell death during infection, we previously utilized a transposon insertion mutant library of E. piscicida to identify mutants that induce membraneruptured cell death based on cell morphology changes and LDH release (Chen et al, 2018;Wen et al, 2019). A novel E. piscicida mutant which was named 1906I was found to trigger cell death in HeLa cells upon infection.…”

Section: A Transposon Insertion In E Piscicida Promotes Lytic Cell De...mentioning

confidence: 99%

“…Upon infection, host NLRC4 and NLRP3 can sense E. piscicida type III secretion system needle protein leading to the activation of caspase 1-mediated inflammasomes and triggering pyroptosis, which promotes host immune defense (Chen et al, 2017). Moreover, E. piscicida Trxlp promotes NLRC4 inflammasome activation in macrophages (Xu et al, 2018) while hemolysin provokes non-canonical inflammasome activation and pyroptosis by promoting intracellular sensing of LPS in mammals and fish (Chen et al, 2018;Wen et al, 2019). Conversely, E. piscicida has evolved diverse strategies to inhibit cell death and evade host immune recognition and killing.…”

Section: Introductionmentioning

confidence: 99%

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Dysregulation of Cytosolic c-di-GMP in Edwardsiella piscicida Promotes Cellular Non-Canonical Ferroptosis

Wen

Wang

Chen

et al. 2022

Front. Cell. Infect. Microbiol.

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Programmed cell death plays an important role in modulating host immune defense and pathogen infection. Ferroptosis is a type of inflammatory cell death induced by intracellular iron-dependent accumulation of toxic lipid peroxides. Although ferroptosis has been associated with cancer and other sterile diseases, very little is known about the role of ferroptosis in modulating host-pathogen interactions. We show that accumulation of the secondary messenger bis-(3′,5′)-cyclic dimeric GMP (c-di-GMP) in the pathogenic bacterium Edwardsiella piscicida (E. piscicida) triggers a non-canonical ferroptosis pathway in infected HeLa cells. Moreover, we observed that the dysregulation of c-di-GMP in E. piscicida promotes iron accumulation, mitochondrial dysfunction, and production of reactive oxygen species, all of which that can be blocked by iron chelator. Importantly, unlike classical ferroptosis that is executed via excess lipid peroxidation, no lipid peroxidation was detected in the infected cells. Furthermore, lipoxygenases inhibitors and lipophilic antioxidants are not able to suppress morphological changes and cell death induced by E. piscicida mutant producing excess c-di-GMP, and this c-di-GMP dysregulation attenuates bacterial virulence in vivo. Collectively, our results reveal a novel non-canonical ferroptosis pathway mediated by bacterial c-di-GMP and provide evidence for a role of ferroptosis in the regulation of pathogen infection.

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Section: Cell Death Assaymentioning

confidence: 99%

Section: A Transposon Insertion In E Piscicida Promotes Lytic Cell De...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dysregulation of Cytosolic c-di-GMP in Edwardsiella piscicida Promotes Cellular Non-Canonical Ferroptosis

Wen

Wang

Chen

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Thus, two strategies were selected to increase the transportation of exogenous choline in this study. The first strategy was the overexpression of a high-affinity choline transporter ScHnm1 from yeast (Fernández- Murray, Gaspard, Jesch, & McMaster, 2009;Murray & McMaster, 2005;Nikawa, Hosaka, Tsukagoshi, & Yamashita, 1990;Nikawa, Tsukagoshi, & Yamashita, 1986); and the second was the expression of a hemolysin consisting of the precursor EthA and the activator EthB from Edwardsiella piscicida, that serves the function of cell binding lysis and cell perforation (J. D. Chen, Lai, & Huang, 1996;Hirono, Tange & Aoki, 1997;Wen et al, 2019).…”

Section: Facilitation Of Cdp-choline Production By the Increase In mentioning

confidence: 99%

Engineering substrate and energy metabolism for living cell production of cytidine‐5′‐diphosphocholine

Ren

Liu

et al. 2020

Biotech & Bioengineering

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Cytidine‐5′‐diphosphocholine (CDP‐choline) is a widely used neuroprotective drug for multiple indications. In industry, CDP‐choline is synthesized by a two‐step cell culture/permeabilized cell biotransformation method because substrates often do not enter cells in an efficient manner. This study develops a novel one‐step living cell fermentation method for CDP‐choline production. For this purpose, the feasibility of Pichia pastoris as a chassis was demonstrated by substrate feeding and CDP‐choline production. Overexpression of choline phosphate cytidylyltransferase and choline kinase enhanced the choline transformation pathway and improved the biosynthesis of CDP‐choline. Furthermore, co‐overexpression of ScHnm1, which is a heterologous choline transporter, highly improved the utilization of choline substrates, despite its easy degradation in cells. This strategy increased CDP‐choline titer by 55‐folds comparing with the wild‐type (WT). Overexpression of cytidine‐5′‐monophosphate (CMP) kinase and CDP kinase in the CMP transformation pathway showed no positive effects. An increase in the ATP production by citrate stimulation or metabolic pathway modification further improved CDP‐choline biosynthesis by 120%. Finally, the orthogonal optimization of key substrates and pH was carried out, and the resulting CDP‐choline titer (6.0 g/L) at optimum conditions increased 88 times the original titer in the WT. This study provides a new paradigm for CDP‐choline bioproduction by living cells.

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“…Zebrafish inflammasomes have also been studied in the infection course of pathogens with high impact on aquaculture. In the zebrafish– Edwarsiella piscicida infection model, bacterial haemolysin can activate a Caspb-dependent pyroptotic activity in non-phagocyte cells [75], and an Asc-independent activation of Caspb, but not Caspa, is important for an efficient host defense [42].…”

Section: Zebrafish Models Of Inflammasome Regulation In Health Andmentioning

confidence: 99%

Zebrafish in Inflammasome Research

Forn-Cuní

Meijer

Varela

2019

Cells

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Inflammasomes are cytosolic multiprotein complexes that regulate inflammatory responses to danger stimuli and infection, and their dysregulation is associated with an increasing number of autoinflammatory diseases. In recent years, zebrafish models of human pathologies to study inflammasome function in vivo have started to emerge. Here, we discuss inflammasome research in zebrafish in light of current knowledge about mammalian inflammasomes. We summarize the evolutionary conservation of inflammasome components between zebrafish and mammals, highlighting the similarities and possible divergence in functions of these components. We present new insights into the evolution of the caspase-1 family in the teleost lineage, and how its evolutionary origin may help contextualize its functions. We also review existing infectious and non-infectious models in zebrafish in which inflammasomes have been directly implicated. Finally, we discuss the advantages of zebrafish larvae for intravital imaging of inflammasome activation and summarize available tools that will help to advance inflammasome research.

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Dysregulated haemolysin promotes bacterial outer membrane vesicles-induced pyroptotic-like cell death in zebrafish

Cited by 11 publications

References 51 publications

Dysregulation of Cytosolic c-di-GMP in Edwardsiella piscicida Promotes Cellular Non-Canonical Ferroptosis

Dysregulation of Cytosolic c-di-GMP in Edwardsiella piscicida Promotes Cellular Non-Canonical Ferroptosis

Engineering substrate and energy metabolism for living cell production of cytidine‐5′‐diphosphocholine

Zebrafish in Inflammasome Research

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