Etx-Y71A as a non-toxic mutant of Clostridium perfringens epsilon toxin induces protective immunity in mice and sheep

Jiang, Zhigang; Chang, Jitao; Wang, Fang; Qi, Yinglin; Li, Yixin; Yu, Debin; Yu, Li

doi:10.1016/j.vaccine.2020.08.002

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…The mutation of H149 and F92 residues within or surrounding the β-octyl glucoside binding site results in a modest reduction in toxicity [ 34 , 83 ]. Other residues such as Y71 [ 83 , 84 ], which is located in domain III, have also been targeted for mutagenesis and may play a role in pore formation.…”

Section: Exploiting Information On the Mode Of Actionmentioning

confidence: 99%

The Molecular Architecture and Mode of Action of Clostridium perfringens ε-Toxin

Titball

2024

Toxins

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Clostridium perfringens ε-toxin has long been associated with a severe enterotoxaemia of livestock animals, and more recently, was proposed to play a role in the etiology of multiple sclerosis in humans. The remarkable potency of the toxin has intrigued researchers for many decades, who suggested that this indicated an enzymatic mode of action. Recently, there have been major breakthroughs by finding that it is a pore-forming toxin which shows exquisite specificity for cells bearing the myelin and lymphocyte protein (MAL) receptor. This review details the molecular structures of the toxin, the evidence which identifies MAL as the receptor and the possible roles of other cell membrane components in toxin binding. The information on structure and mode of action has allowed the functions of individual amino acids to be investigated and has led to the creation of mutants with reduced toxicity that could serve as vaccines. In spite of this progress, there are still a number of key questions around the mode of action of the toxin which need to be further investigated.

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Section: Exploiting Information On the Mode Of Actionmentioning

confidence: 99%

The Molecular Architecture and Mode of Action of Clostridium perfringens ε-Toxin

Titball

2024

Toxins

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“…Escherichia coli (E. coli) BL21 (DE3) has been routinely used as an expression system to produce recombinant C. perfringens toxins (Lobato et al, 2010;Li et al, 2013;Jiang et al, 2020) and the SUMO-tag can significantly enhance protein stability and solubility in prokaryotic production systems (Nagahama et al, 2003). Considering the high AT content of the C. perfringens genome, related sequences are typically optimized according to the codon usage of E. coli (Nagahama et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

A non-toxic recombinant protein rSUMO-CPBm4 as a potential vaccine candidate against Clostridium perfringens type C beta enterotoxemia

2023

Trop Biomed

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Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPB m4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPB m4 (rSUMO-CPB m4 ) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPB m4 , rSUMO-CPB m4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPB m4 nor rSUMO-CPB m4 was lethal to mice. Although rCPB m4 and rSUMO-CPB m4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPB m4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPB m4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.

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A non-toxic recombinant Clostridium septicum α toxin induces protective immunity in mice and rabbits

Meki

et al. 2023

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Etx-Y71A as a non-toxic mutant of Clostridium perfringens epsilon toxin induces protective immunity in mice and sheep

Cited by 5 publications

References 33 publications

The Molecular Architecture and Mode of Action of Clostridium perfringens ε-Toxin

The Molecular Architecture and Mode of Action of Clostridium perfringens ε-Toxin

A non-toxic recombinant protein rSUMO-CPBm4 as a potential vaccine candidate against Clostridium perfringens type C beta enterotoxemia

A non-toxic recombinant Clostridium septicum α toxin induces protective immunity in mice and rabbits

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