Clostridium tetani
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA35235 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| DRR015946_1.fastq.gz | Fastqsanger.gz | |||
| DRR015946_2.fastq.gz | Fastqsanger.gz | |||
| DRR403812_1.fastq.gz | Fastqsanger.gz | |||
| DRR403812_2.fastq.gz | Fastqsanger.gz |
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Project description:Clostridium tetani produces the tetanus-causing tetanus toxin (TeNT), one of the most powerful bacterial toxins known to humankind. The regulation of toxin expression is complex and involves the alternative sigma factor TetR as well as other regulators. Here, we identified a novel regulatory molecule, a non-coding small regulatory RNA (sRNA), located in the 3’ untranslated region of the tent gene. We show with an antisense RNA approach and recombinant expression of the tent locus with and without the sRNA in C. tetani strains that the sRNA acts as a negative regulator of TeNT expression and modulates the growth pattern of C. tetani. Its possible role is to limit tetanus toxin levels in the exponential growth phase; thus, it might interlock bacterial growth and toxin production.
2020-07-31 | GSE150141 | GEO
Project description:We used RNA-seq to determine Clostridium tetani gene expression changes in response to culture conditions and time. Changes in response to time were more pronounced than those in response to culture conditions. The tetanus toxin gene is always highly expressed but does show expression changes between culture conditions. These results may become part of an approach to reduce animal testing during vaccine manufacturing.
2022-01-02 | GSE182408 | GEO
Project description:To develop a method for improved assessment of the genetic stability of bacterial vaccine strains, we applied next-generation sequencing to a Clostridium tetani model strain (including inter- and intra-lab replicates) and other strains. Data were processed to determine (gain or loss of) gene copy numbers. Strains could easily be distiguished based on gain/loss of prophage-like and CRISPR/Cas genes. We found that the model strain has multiple copies of the plasmid carrying the gene coding for tetanus toxin as well as several other genes. Data were reproducible within and between laboratories. The limit of detection of our method is an order of magnitude better than that of the pulsed-field gel electrophoresis (PFGE) currently used during manufacturing. This approach may part of an approach to reduce animal testing during vaccine manufacturing.
2020-02-15 | GSE144242 | GEO
Project description: Not available
| S-EPMC4178411 | biostudies-literature
Project description:Clostridium tetani and Clostridium botulinum produce two of the most potent neurotoxins known, tetanus neurotoxin and botulinum neurotoxin, respectively. Extensive biochemical and genetic investigation has been devoted to identifying and characterizing various C. botulinum strains. Less effort has been focused on studying C. tetani likely because recently sequenced strains of C. tetani show much less genetic diversity than C. botulinum strains and because widespread vaccination efforts have reduced the public health threat from tetanus. Our aim was to acquire genomic data on the U.S. vaccine strain of C. tetani to better understand its genetic relationship to previously published genomic data from European vaccine strains. We performed high throughput genomic sequence analysis on two wild-type and two vaccine C. tetani strains. Comparative genomic analysis was performed using these and previously published genomic data for seven other C. tetani strains. Our analysis focused on single nucleotide polymorphisms (SNP) and four distinct constituents of the mobile genome (mobilome): a hypervariable flagellar glycosylation island region, five conserved bacteriophage insertion regions, variations in three CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems, and a single plasmid. Intact type IA and IB CRISPR/Cas systems were within 10 of 11 strains. A type IIIA CRISPR/Cas system was present in two strains. Phage infection histories derived from CRISPR-Cas sequences indicate C. tetani encounters phages common among commensal gut bacteria and soil-borne organisms consistent with C. tetani distribution in nature. All vaccine strains form a clade distinct from currently sequenced wild type strains when considering variations in these mobile elements. SNP, flagellar glycosylation island, prophage content and CRISPR/Cas phylogenic histories provide tentative evidence suggesting vaccine and wild type strains share a common ancestor.
| S-EPMC5553647 | biostudies-literature
Project description:Eukaryotic F-actin is constructed from two protofilaments that gently wind around each other to form a helical polymer. Several bacterial actin-like proteins (Alps) are also known to form F-actin-like helical arrangements from two protofilaments, yet with varied helical geometries. Here, we report a unique filament architecture of Alp12 from Clostridium tetani that is constructed from four protofilaments. Through fitting of an Alp12 monomer homology model into the electron microscopy data, the filament was determined to be constructed from two antiparallel strands, each composed of two parallel protofilaments. These four protofilaments form an open helical cylinder separated by a wide cleft. The molecular interactions within single protofilaments are similar to F-actin, yet interactions between protofilaments differ from those in F-actin. The filament structure and assembly and disassembly kinetics suggest Alp12 to be a dynamically unstable force-generating motor involved in segregating the pE88 plasmid, which encodes the lethal tetanus toxin, and thus a potential target for drug design. Alp12 can be repeatedly cycled between states of polymerization and dissociation, making it a novel candidate for incorporation into fuel-propelled nanobiopolymer machines.
| S-EPMC3375535 | biostudies-literature
Project description:We sequenced the genome of a Clostridium tetani strain that caused chronic tibial osteitis without any clinical sign of tetanus in a 26-year-old man previously vaccinated against this disease. The genome contained a plasmid that harboured the tetX-tetR tetanospasmin operon, and was highly similar to that of a tetanus-causing strain.
| S-EPMC4184619 | biostudies-literature
Project description:Ensuring consistency of tetanus neurotoxin (TeNT) production by Clostridium tetani could help to ensure consistent product quality in tetanus vaccine manufacturing, ultimately contributing to reduced animal testing. The aim of this study was to identify RNA signatures related to consistent TeNT production using standard and non-standard culture conditions. We applied RNA sequencing (RNA-Seq) to study C. tetani gene expression in small-scale batches under several culture conditions. We identified 1381 time-dependent differentially expressed genes (DEGs) reflecting, among others, changes in growth rate and metabolism. Comparing non-standard versus standard culture conditions identified 82 condition-dependent DEGs, most of which were specific for one condition. The tetanus neurotoxin gene (tetX) was highly expressed but showed expression changes over time and between culture conditions. The tetX gene showed significant down-regulation at higher pH levels (pH 7.8), which was confirmed by the quantification data obtained with the recently validated targeted LC-MS/MS approach. Non-standard culture conditions lead to different gene expression responses. The tetX gene appears to be the best transcriptional biomarker for monitoring TeNT production as part of batch-to-batch consistency testing during tetanus vaccine manufacturing.
| S-EPMC8778922 | biostudies-literature
Project description:Whole genome analysis of Clostridium tetani strains isolated in Japan
| PRJDB14332 | ENA