The population structure of Clostridium tetani deduced from its pan-genome

Chapeton-Montes, Diana; Plourde, Lucile; Bouchier, Christiane; Ma, Laurence; Diancourt, Laure; Criscuolo, Alexis; Popoff, Michel R.; Brüggemann, Holger

doi:10.1038/s41598-019-47551-4

Cited by 21 publications

(31 citation statements)

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“…One serotype of TeNT is known, whilst eight different serotypes of BoNT have been characterized (BoNT/A, /B, /C, /D, /E, /F, /G, and /X) [2,8]. TeNT proteins with little variation in amino acid sequence, that do not alter significantly their antigenicity, have been recently reported [9,10], whereas many dozens of BoNTs with very variable primary structures and ensuing different biological properties and antigenicity have been described. They are defined as subtypes of a given serotype and indicated with arabic numbers (for example BoNT/A1, BoNT/A2, etc.)…”

Section: Clostridial Neurotoxinsmentioning

confidence: 99%

Tables of Toxicity of Botulinum and Tetanus Neurotoxins

Rossetto

Montecucco

2019

Toxins

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Tetanus and botulinum neurotoxins are the most poisonous substances known, so much so as to be considered for a possible terrorist use. At the same time, botulinum neurotoxin type A1 is successfully used to treat a variety of human syndromes characterized by hyperactive cholinergic nerve terminals. The extreme toxicity of these neurotoxins is due to their neurospecificity and to their metalloprotease activity, which results in the deadly paralysis of tetanus and botulism. Recently, many novel botulinum neurotoxins and some botulinum-like toxins have been discovered. This large number of toxins differs in terms of toxicity and biological activity, providing a potential goldmine for novel therapeutics and for new molecular tools to dissect vesicular trafficking, fusion, and exocytosis. The scattered data on toxicity present in the literature require a systematic organization to be usable by scientists and clinicians. We have assembled here the data available in the literature on the toxicity of these toxins in different animal species. The internal comparison of these data provides insights on the biological activity of these toxins.

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Section: Clostridial Neurotoxinsmentioning

confidence: 99%

Tables of Toxicity of Botulinum and Tetanus Neurotoxins

Rossetto

Montecucco

2019

Toxins

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“…The 114 nt sequence of the putative sRNA was identified also in all other plasmid-positive Harvard-derived strains clade 1A strains, according to 22 , such as E88, CN655, and strain A with a 100% identity on nucleotide level. In addition, all plasmid-positive C. tetani strains of clades 1B to 1E carry an identical sequence (with strain TMB2, a clade 1B strain, as the only exception) (Sup.…”

Section: Resultsmentioning

confidence: 88%

“…S2 ). We took advantage of the strain 1586-Z1, which is a non-toxigenic derivative of the clade 1A strain 1586-U1 22 . Both strains, 1586-Z1 and 1586-U1, retain the same chromosomal genome sequence, but 1586-Z1 lacks the wild-type large plasmid harboring tent 22 .…”

Section: Resultsmentioning

confidence: 99%

“…We took advantage of the strain 1586-Z1, which is a non-toxigenic derivative of the clade 1A strain 1586-U1 22 . Both strains, 1586-Z1 and 1586-U1, retain the same chromosomal genome sequence, but 1586-Z1 lacks the wild-type large plasmid harboring tent 22 . The recombinant plasmids p1423 and p1424 were transformed into 1586-Z1 to compare the expression of the recombinant tetR-tent genes, with and without the putative sRNA in a C. tetani genomic background.…”

Section: Resultsmentioning

confidence: 99%

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Identification of a non-coding RNA and its putative involvement in the regulation of tetanus toxin synthesis in Clostridium tetani

Brüggemann

Chapeton-Montes

Plourde

et al. 2021

Sci Rep

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Clostridium tetani produces the tetanus toxin (TeNT), one of the most powerful bacterial toxins known to humankind and responsible for tetanus. The regulation of toxin expression is complex and involves the alternative sigma factor TetR as well as other regulators. Here, a transcriptional analysis of the TeNT-encoding large plasmid of C. tetani identified a putative non-coding small RNA (sRNA), located in close vicinity of the 3′ untranslated region of the tent gene. A northern blot experiment could identify a respective sRNA with a size of approx. 140 nucleotides. Sequence analysis showed that the sRNA contains a 14-nucleotide region that is complementary to a 5′ located region of tent. In order to investigate the function of the sRNA, we applied a RNA interference approach targeting the sRNA in two C. tetani wild-type strains; the constructed antisense C. tetani strains showed an approx. threefold increase in both extracellular and total TeNT production compared to the respective wild-type strains. In addition, recombinant C. tetani strains were constructed that contained tent-locus harboring plasmids with and without the sRNA. However, the introduction of the tent-locus without the sRNA in a C. tetani strain lacking the wild-type TeNT-encoding large plasmid resulted in a lower TeNT production compared to the same strain with recombinant tent-locus with the sRNA. This suggests that the expression or the effect of the sRNA is modulated by the C. tetani genetic background, notably that of the wild-type TeNT-encoding large plasmid. In addition, some recombinant strains exhibited modulated growth patterns, characterized by premature bacterial cell lysis. Taken together, our data indicate that the sRNA acts as a negative regulator of TeNT synthesis, with a possible impact on the growth of C. tetani. We hypothesize that the role of this sRNA is to limit toxin levels in the exponential growth phase in order to prevent premature bacterial lysis.

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“…The genome contains a chromosome of approximately 2.8 Mb and a TeNT-encoding plasmid of 74 kb. The genomes of additional C. tetani strains have been sequenced and showed that the plasmid-encoded tent is highly conserved [10][11][12]. A conserved gene (tetR, tetanus toxin regulatory gene) just upstream of tent encodes for an alternative sigma factor which positively regulates the transcription of tent [13].…”

Section: Introductionmentioning

confidence: 99%

Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes in Clostridium tetani

Chapeton-Montes

Plourde

Denève

et al. 2020

Toxins

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Clostridium tetani produces a potent neurotoxin, the tetanus toxin (TeNT), which is responsible for an often-fatal neurological disease (tetanus) characterized by spastic paralysis. Prevention is efficiently acquired by vaccination with the TeNT toxoid, which is obtained by C. tetani fermentation and subsequent purification and chemical inactivation. C. tetani synthesizes TeNT in a regulated manner. Indeed, the TeNT gene (tent) is mainly expressed in the late exponential and early stationary growth phases. The gene tetR (tetanus regulatory gene), located immediately upstream of tent, encodes an alternative sigma factor which was previously identified as a positive regulator of tent. In addition, the genome of C. tetani encodes more than 127 putative regulators, including 30 two-component systems (TCSs). Here, we investigated the impact of 12 regulators on TeNT synthesis which were selected based on their homology with related regulatory elements involved in toxin production in other clostridial species. Among nine TCSs tested, three of them impact TeNT production, including two positive regulators that indirectly stimulate tent and tetR transcription. One negative regulator was identified that interacts with both tent and tetR promoters. Two other TCSs showed a moderate effect: one binds to the tent promoter and weakly increases the extracellular TeNT level, and another one has a weak inverse effect. In addition, CodY (control of dciA (decoyinine induced operon) Y) but not Spo0A (sporulation stage 0) or the DNA repair protein Mfd (mutation frequency decline) positively controls TeNT synthesis by interacting with the tent promoter. Moreover, we found that inorganic phosphate and carbonate are among the environmental factors that control TeNT production. Our data show that TeNT synthesis is under the control of a complex network of regulators that are largely distinct from those involved in the control of toxin production in Clostridium botulinum or Clostridium difficile.

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The population structure of Clostridium tetani deduced from its pan-genome

Cited by 21 publications

References 50 publications

Tables of Toxicity of Botulinum and Tetanus Neurotoxins

Tables of Toxicity of Botulinum and Tetanus Neurotoxins

Identification of a non-coding RNA and its putative involvement in the regulation of tetanus toxin synthesis in Clostridium tetani

Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes in Clostridium tetani

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