Tetanus in animals

Tetanus is a neurologic disease of humans and animals characterized by spastic paralysis. Tetanus is caused by tetanus toxin (TeNT) produced by Clostridium tetani, an environmental soilborne, gram-positive, sporulating bacterium. The disease most often results from wound contamination by soil containing C. tetani spores. Horses, sheep, and humans are highly sensitive to TeNT, whereas cattle, dogs, and cats are more resistant. The diagnosis of tetanus is mainly based on the characteristic clinical signs. Identification of C. tetani at the wound site is often difficult.

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

Toxins ◽

10.3390/toxins12050328 ◽

2020 ◽

Vol 12 (5) ◽

pp. 328

Author(s):

Diana Chapeton-Montes ◽

Lucile Plourde ◽

Cecile Deneve ◽

Dominique Garnier ◽

Fabien Barbirato ◽

...

Keyword(s):

Complex Network ◽

Tetanus Toxin ◽

Regulatory Gene ◽

Toxin Production ◽

Regulatory Elements ◽

Negative Regulator ◽

Clostridium Tetani ◽

Spastic Paralysis ◽

Clostridial Species ◽

The Impact

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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Tetanus in Animals — Summary of Knowledge

Folia Veterinaria ◽

10.2478/fv-2020-0027 ◽

2020 ◽

Vol 64 (3) ◽

pp. 54-60

Author(s):

Z. Malinovská ◽

E. Čonková ◽

P. Váczi

Keyword(s):

Supportive Care ◽

Animal Species ◽

Clinical Signs ◽

Bacterial Disease ◽

Considerable Variability ◽

Clostridium Tetani ◽

Spastic Paralysis ◽

Penetrating Wounds ◽

Characteristic Sign ◽

Transmissible Disease

AbstractTetanus is a neurologic non-transmissible disease (often fatal) of humans and other animals with a worldwide occurrence. Clostridium tetani is the spore producing bacillus which causes the bacterial disease. In deep penetrating wounds the spores germinate and produce a toxin called tetanospasmin. The main characteristic sign of tetanus is a spastic paralysis. A diagnosis is usually based on the clinical signs because the detection in the wound and the cultivation of C. tetani is very difficult. Between animal species there is considerable variability in the susceptibility to the bacillus. The most sensitive animal species to the neurotoxin are horses. Sheep and cattle are less sensitive and tetanus in these animal species are less common. Tetanus in cats and dogs are rare and dogs are less sensitive than cats. Clinically two forms of tetanus have been recognized, i. e. localized and generalized. The available treatment is not specific because the toxin in neuronal cells cannot be accessed by antitoxin antibodies. The aim of the therapy is to: neutralise the unbound neurotoxin, inhibit C. tetani growth in the wound, and provide supportive care to mitigate the effects of the neurotoxin. The treatment is difficult with an unclear prognosis.

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Toxicity of papain-digested tetanus toxin. Pathological effect of fragment B in the absence of spastic paralysis.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)38278-9 ◽

1978 ◽

Vol 253 (1) ◽

pp. 125-129

Author(s):

T.B. Helting ◽

H.J. Ronneberger ◽

R. Vollerthun ◽

V. Neubauer

Keyword(s):

Tetanus Toxin ◽

Pathological Effect ◽

Spastic Paralysis

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Combining vancomycin-modified gold nanorod arrays and colloidal nanoparticles as the sandwich model for discrimination of gram-positive bacteria and their detection via surface-enhanced Raman spectroscopy (SERS)

The Analyst ◽

10.1039/d1an00321f ◽

2021 ◽

Author(s):

Araz Norouz Dizaji ◽

Nihal Simsek Ozek ◽

Ferhunde Aysin ◽

Ayfer Calis ◽

Asli Yilmaz ◽

...

Keyword(s):

Raman Spectroscopy ◽

Surface Enhanced Raman Spectroscopy ◽

Colloidal Nanoparticles ◽

Nanorod Arrays ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Sensor Platform ◽

Highly Sensitive ◽

Surface Enhanced ◽

Surface Enhanced Raman

This study reports the development of a highly sensitive antibiotic-based discrimination and sensor platform for the detection of gram-positive bacteria through surface-enhanced Raman spectroscopy (SERS). Herein, the combination of gold...

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Degenerative axonopathy associated with copper deficiency in pigs

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2017000900002 ◽

2017 ◽

Vol 37 (9) ◽

pp. 911-915 ◽

Cited By ~ 1

Author(s):

Roberio G. Olinda ◽

Lisanka A. Maia ◽

Maria T.S. Frade ◽

Mauro P. Soares ◽

Severo S. Barros ◽

...

Keyword(s):

White Matter ◽

Purkinje Cells ◽

Copper Deficiency ◽

Clinical Signs ◽

Atomic Absorption Spectrophotometry ◽

Semiarid Region ◽

Spastic Paralysis ◽

Myelin Sheaths ◽

Cu Deficiency ◽

Spinal Segments

ABSTRACT: The epidemiological, clinic and morphological (pathological and ultrastructural) aspects of four outbreaks of copper deficiency affecting 21- to 90-day-old pigs in the Northeast region of Brazil are reported. Clinical signs began with paraparesis and ataxia and progressed to flaccid or spastic paralysis of the pelvic and thoracic limbs, followed by sternal and/or lateral recumbence. In addition, some animals showed dog-sitting position and intention tremors. The clinical manifestation period was 5-20 days. Significant gross lesions were not observed; however, microscopically, symmetrical degeneration of the white matter with ballooned myelin sheaths containing occasional macrophages was observed, mainly in the spinal cord. Two pigs presented with necrosis ad loss of Purkinje cells and ectopic Purkinje cells in the granular layer and cerebellar white matter. A ultrastructural analysis showed different degrees of damage of myelinated axons in the spinal segments, including an absence of the axoplasm structures with only axonal residues remaining. The myelin sheaths were degenerated and often collapsed into the space previously occupied by the axon. These results suggest that myelin degeneration is secondary to the axonal lesion. Finally, the concentration of copper in the liver was determined using atomic absorption spectrophotometry and was found to be low (ranging from 2.2 to 10.8 ppm). In conclusion, in the Brazilian semiarid region, Cu deficiency occurs in 21 to 90-day-old pigs that ingested different types of waste in their food.

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Tetanus

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0127 ◽

2020 ◽

pp. 1109-1115

Author(s):

C. Louise Thwaites ◽

Lam Minh Yen

Keyword(s):

Nervous System ◽

Autonomic Nervous System ◽

Developed Countries ◽

Significant Problem ◽

Clostridium Tetani ◽

Autonomic Nervous System Dysfunction ◽

Autonomic Nervous ◽

Highly Sensitive ◽

Muscle Spasms ◽

Treatment Mortality

Clostridium tetani is a Gram-positive spore-forming anaerobic bacillus able to infect and cause disease in both humans and animals. The bacterium is highly sensitive to oxygen but can survive in the environment as an extremely resistant metabolically inactive spore. Under suitable anaerobic conditions the spore germinates and the bacteria multiply, releasing a highly potent neurotoxin, tetanus toxin, which is responsible for the clinical features of tetanus. Tetanus is a disease characterized by muscle spasms caused by a toxin produced by Clostridium tetani. Without treatment mortality is high due to muscle spasms which prevent respiration or due cardiovascular system instability secondary to autonomic nervous system dysfunction. Tetanus is prevented by good wound hygiene and/or vaccination and, although rare in developed countries, the disease remains a significant problem in many countries where facilities for treatment are often poor and mortality remains high.

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Outbreak of Clostridium perfringens type D enterotoxemia in sheep

Semina Ciências Agrárias ◽

10.5433/1679-0359.2019v40n6p2593 ◽

2019 ◽

Vol 40 (6) ◽

pp. 2593

Author(s):

Felipe Masiero Salvarani ◽

Mayane Faccin ◽

Nayra Fernanda de Queiroz Ramos Freitas ◽

Mônica Regina de Matos ◽

Edismair Carvalho Garcia ◽

...

Keyword(s):

Clostridium Perfringens ◽

Clinical Signs ◽

Necrotic Enteritis ◽

Spastic Paralysis ◽

Type D ◽

Laboratory Confirmation ◽

Intestinal Contents ◽

Epsilon Toxin ◽

History Of ◽

Diagnostic Modalities

This work describes the first Brazilian laboratory-confirmed outbreak of enterotoxemia caused by Clostridium perfringens type D in sheep, which occurred in the state of Paraná. We address the epidemiological aspects involved, the diagnostic modalities employed, and the clinical signs and pathological findings observed. Eight healthy pregnant female sheep with no history of vaccination for clostridiosis presented with a history of abrupt feeding changes and neurological manifestations that quickly evolved to illness, coma and death. Four other females with clinical neurological signs were referred to the Veterinary Hospital of the Universidade Federal do Paraná, Palotina Sector. These animals presented with lethargy, motor incoordination, opisthotonus, pedal movements, muscle tremors, spastic paralysis, bruxism, mandibular trismus, sialorrhea, hyperexcitability and the inability to stand. They were examined and euthanized due to the seriousness of the clinical picture with an unfavorable prognosis. We performed gross anatomical and microscopic analyses of the organs and intestinal contents. We also performed bacterial isolation with molecular typing. From the intestinal contents, we detected toxins by means of the seroneutralization technique in mice. At necropsy, we noted pulmonary edema (2/4), necrotizing enteritis (4/4) and hyperemia of the leptomeninges (1/4). Microscopically, we observed lymphohistiocytic interstitial pneumonia, necrotic enteritis associated with the presence of rods, and nephrosis with interstitial lymphohistiocytic nephritis. No significant brain lesions were observed. Using serum neutralization, we identified epsilon toxin in the intestinal contents of all four animals. C. perfringens type D was identified. Based on the history, clinical signs, postmortem findings, and laboratory confirmation of the presence of epsilon toxin, we concluded that C. perfringens type D enterotoxemia caused this outbreak of sheep deaths.

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A Heterologous Reporter Defines the Role of the Tetanus Toxin Interchain Disulfide in Light-Chain Translocation

Infection and Immunity ◽

10.1128/iai.00477-15 ◽

2015 ◽

Vol 83 (7) ◽

pp. 2714-2724 ◽

Cited By ~ 9

Author(s):

Madison Zuverink ◽

Chen Chen ◽

Amanda Przedpelski ◽

Faith C. Blum ◽

Joseph T. Barbieri

Keyword(s):

Motor Neurons ◽

Disulfide Bond ◽

Light Chain ◽

Tetanus Toxin ◽

Thioredoxin Reductase ◽

Single Chain ◽

Intact Cells ◽

Spastic Paralysis ◽

Interchain Disulfide Bond ◽

N Terminus

Botulinum neurotoxins (BoNTs) and tetanus toxin (TeNT) are the most potent toxins for humans and elicit unique pathologies due to their ability to traffic within motor neurons. BoNTs act locally within motor neurons to elicit flaccid paralysis, while retrograde TeNT traffics to inhibitory neurons within the central nervous system (CNS) to elicit spastic paralysis. BoNT and TeNT are dichain proteins linked by an interchain disulfide bond comprised of an N-terminal catalytic light chain (LC) and a C-terminal heavy chain (HC) that encodes an LC translocation domain (HCT) and a receptor-binding domain (HCR). LC translocation is the least understood property of toxin action, but it involves low pH, proteolysis, and an intact interchain disulfide bridge. Recently, Pirazzini et al. (FEBS Lett 587:150–155, 2013,http://dx.doi.org/10.1016/j.febslet.2012.11.007) observed that inhibitors of thioredoxin reductase (TrxR) blocked TeNT and BoNT action in cerebellar granular neurons. In the current study, an atoxic TeNT LC translocation reporter was engineered by fusing β-lactamase to the N terminus of TeNT [βlac-TeNT(RY)] to investigate LC translocation in primary cortical neurons and Neuro-2a cells. βlac-TeNT(RY) retained the interchain disulfide bond, showed ganglioside-dependent binding to neurons, required acidification to promote βlac translocation, and was sensitive to auranofin, an inhibitor of thioredoxin reductase. Mutation of βlac-TeNT(RY) at C439S and C467S eliminated the interchain disulfide bond and inhibited βlac translocation. These data support the requirement of an intact interchain disulfide for LC translocation and imply that disulfide reduction is a prerequisite for LC delivery into the host cytosol. The data also support a model that LC translocation proceeds from the C to the N terminus. βlac-TeNT(RY) is the first reporter system to measure translocation by an AB single-chain toxin in intact cells.

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