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Epsilon Toxin-Producing Clostridium perfringens within the MS Gut Microbiome and Epsilon Toxin Function on Immune Privilege

ABSTRACT: Epsilon Toxin-Producing Clostridium perfringens within the MS Gut Microbiome and Epsilon Toxin Function on Immune Privilege

PROVIDER: PRJNA925123 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23109714_1.fastq.gz	Fastqsanger.gz
	SRR23109714_2.fastq.gz	Fastqsanger.gz
	SRR23109715_1.fastq.gz	Fastqsanger.gz
	SRR23109715_2.fastq.gz	Fastqsanger.gz
	SRR23109716_1.fastq.gz	Fastqsanger.gz

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Epsilon Toxin-Producing Clostridium perfringens within the MS Gut Microbiome and Epsilon Toxin Function on Immune Privilege

Project description:Multiple Sclerosis (MS) is a complex disease of the CNS believed to require one or more environmental triggers and is characterized by episodic formation of inflammatory demyelinating lesions in the brain and spinal cord. Gut dysbiosis is a common feature in MS and here, using enhanced and quantitative PCR detection, we show that people with MS are more likely to harbor and have higher abundance of epsilon toxin (ETX)-producing strains of Clostridium perfringens within their gut microbiome compared to healthy controls (HC). MS patient-derived isolates produce functional ETX and have a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, we find that ETX can substitute for PTX in disease induction. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE results in multifocal demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the lesion distribution observed in MS. Transcriptional profiles from CNS endothelial cells reveal ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings support ETX-producing strains of C. perfringens as biologically plausible pathogens in MS to trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.

2023-03-31 | GSE223137 | GEO

Genome-wide transcriptomic analysis of duodenum in broilers infused with crude Clostridium perfringens toxin in situ

Project description:We use a genome wide transcriptomic approach to assess the effects of C. perfringens toxin infusion in the duodenum of broilers

2015-05-31 | E-MTAB-1028 | biostudies-arrayexpress

Epsilon toxin-producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege.

Project description:Multiple sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specific causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection to show that people with MS were more likely to harbor and show a greater abundance of epsilon toxin-producing (ETX-producing) strains of C. perfringens within their gut microbiomes compared with individuals who are healthy controls (HCs). Isolates derived from patients with MS produced functional ETX and had a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, ETX can substitute for PTX. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE caused demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the neuroanatomical lesion distribution seen in MS. CNS endothelial cell transcriptional profiles revealed ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings suggest that ETX-producing C. perfringens strains are biologically plausible pathogens in MS that trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.

| S-EPMC10145940 | biostudies-literature

Project description:Epsilon toxin producing Clostridium perfringens strains

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The pore structure of Clostridium perfringens epsilon toxin.

Project description:Epsilon toxin (Etx), a potent pore forming toxin (PFT) produced by Clostridium perfringens, is responsible for the pathogenesis of enterotoxaemia of ruminants and has been suggested to play a role in multiple sclerosis in humans. Etx is a member of the aerolysin family of β-PFTs (aβ-PFTs). While the Etx soluble monomer structure was solved in 2004, Etx pore structure has remained elusive due to the difficulty of isolating the pore complex. Here we show the cryo-electron microscopy structure of Etx pore assembled on the membrane of susceptible cells. The pore structure explains important mutant phenotypes and suggests that the double β-barrel, a common feature of the aβ-PFTs, may be an important structural element in driving efficient pore formation. These insights provide the framework for the development of novel therapeutics to prevent human and animal infections, and are relevant for nano-biotechnology applications.

| S-EPMC6572795 | biostudies-literature

Clostridium perfringens

Project description:Identification of Novel toxin homologs of Clostridium perfringens

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Transcriptomic changes associated with DNA pol epsilon deficiency

Project description:What is the impact of DNA pol epsilon deficiency on gene expression as well as on the expression of ncRNA, gene silencing etc.? Plantlets were grown in vitro on half strength MS for 9 days and used for total RNA extraction.

2016-07-22 | GSE71002 | GEO

Transcriptomic changes associated with DNA pol epsilon deficiency

Project description:What is the impact of DNA pol epsilon deficiency on gene expression as well as on the expression of ncRNA, gene silencing? To further investigate the effects of DPB2 over-expression, the transcriptome of DPB2OE lines 1 and 3 was compared to that of wild-type plants by RNA sequencing. Plantlets were grown in vitro on half strength MS for 9 days and used for total RNA extraction. mRNA seq on wild-type Col-0, two DPB2 overexpression lines and one abo4-1 mutant knock out.

2016-07-22 | E-GEOD-71002 | biostudies-arrayexpress

Inhibition of Clostridium perfringens epsilon toxin by β-cyclodextrin derivatives.

Project description:Clostridium perfringens epsilon toxin (ETX) is considered as one of the most dangerous potential biological weapons. The goal of this work was to identify inhibitors of ETX using a novel approach for the inactivation of pore-forming toxins. The approach is based on the blocking of the target pore with molecules having the same symmetry as the pore itself. About 200 various β-cyclodextrin derivatives were screened for inhibitors of ETX activity using a colorimetric cell viability assay. Several compounds with dose-dependent activities at low micromolar concentrations have been identified. The same compounds were also able to inhibit lethal toxin of Bacillus anthracis.

| S-EPMC5623079 | biostudies-literature

Epsilon-toxin plasmids of Clostridium perfringens type D are conjugative.

Project description:Isolates of Clostridium perfringens type D produce the potent epsilon-toxin (a CDC/U.S. Department of Agriculture overlap class B select agent) and are responsible for several economically significant enterotoxemias of domestic livestock. It is well established that the epsilon-toxin structural gene, etx, occurs on large plasmids. We show here that at least two of these plasmids are conjugative. The etx gene on these plasmids was insertionally inactivated using a chloramphenicol resistance cassette to phenotypically tag the plasmid. High-frequency conjugative transfer of the tagged plasmids into the C. perfringens type A strain JIR325 was demonstrated, and the resultant transconjugants were shown to act as donors in subsequent mating experiments. We also demonstrated the transfer of "unmarked" native epsilon-toxin plasmids into strain JIR325 by exploiting the high transfer frequency. The transconjugants isolated in these experiments expressed functional epsilon-toxin since their supernatants had cytopathic effects on MDCK cells and were toxic in mice. Using the widely accepted multiplex PCR approach for toxin genotyping, these type A-derived transconjugants were genotypically type D. These findings have significant implications for the C. perfringens typing system since it is based on the toxin profile of each strain. Our study demonstrated the fluid nature of the toxinotypes and their dependence upon the presence or absence of toxin plasmids, some of which have for the first time been shown to be conjugative.

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