scholarly journals Clostridium Perfringens Type D Epsilon Prototoxin and Toxin Effects on the Mouse Body Weight

2014 ◽  
Vol 2 (3) ◽  
Author(s):  
Reza Pilehchian Langroudi
Keyword(s):  
Body Weight ◽  
Clostridium Perfringens ◽  
Type D ◽  
Mouse Body Weight

scholarly journals CodY Is a Global Regulator of Virulence-Associated Properties for Clostridium perfringens Type D Strain CN3718

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Jihong Li ◽  
Menglin Ma ◽  
Mahfuzur R. Sarker ◽  
Bruce A. McClane
Keyword(s):  
Clostridium Perfringens ◽  
Null Mutant ◽  
Intestinal Infection ◽  
Wild Type ◽  
Global Regulator ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Type D ◽  
Epsilon Toxin ◽  
Virulence Properties

ABSTRACT CodY is known to regulate various virulence properties in several Gram-positive bacteria but has not yet been studied in the important histotoxic and intestinal pathogen Clostridium perfringens. The present study prepared an isogenic codY-null mutant in C. perfringens type D strain CN3718 by insertional mutagenesis using the Targetron system. Western blot analysis indicated that, relative to wild-type CN3718 or a complementing strain, this isogenic codY mutant produces reduced levels of epsilon toxin (ETX). Using supernatants from cultures of the wild-type, codY-null mutant, and complementing strains, CodY regulation of ETX production was shown to have cytotoxic consequences for MDCK cells. The CodY regulatory effect on ETX production was specific, since the codY-null mutant still made wild-type levels of alpha-toxin and perfringolysin O. Sialidase activity measurements and sialidase Western blot analysis of supernatants from CN3718 and its isogenic derivatives showed that CodY represses overall exosialidase activity due to a reduced presence of NanH in culture supernatants. Inactivation of the codY gene significantly decreased the adherence of CN3718 vegetative cells or spores to host Caco-2 cells. Finally, the codY mutant showed increased spore formation under vegetative growth conditions, although germination of these spores was impaired. Overall, these results identify CodY as a global regulator of many C. perfringens virulence-associated properties. Furthermore, they establish that, via CodY, CN3718 coordinately regulates many virulence-associated properties likely needed for intestinal infection. IMPORTANCE Clostridium perfringens is a major human and livestock pathogen because it produces many potent toxins. C. perfringens type D strains cause intestinal infections by producing toxins, especially epsilon toxin (ETX). Previous studies identified CodY as a regulator of certain virulence properties in other Gram-positive bacteria. Our study now demonstrates that CodY is a global regulator of virulence-associated properties for type D strain CN3718. It promotes production of ETX, attachment of CN3718 vegetative cells or spores to host enterocyte-like Caco-2 cells, and spore germination; the last two effects may assist intestinal colonization. In contrast, CodY represses sporulation. These results provide the first evidence that CodY can function as a global regulator of C. perfringens virulence-associated properties and that this strain coordinately regulates its virulence-associated properties using CodY to increase ETX production, host cell attachment, and spore germination but to repress sporulation, as would be optimal during type D intestinal infection.

scholarly journals Intramural Vascular Edema in the Brain of Goats With Clostridium perfringens Type D Enterotoxemia

2019 ◽  
Vol 56 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Joaquín Ortega ◽  
José Manuel Verdes ◽  
Eleonora L. Morrell ◽  
John W. Finnie ◽  
Jim Manavis ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Periodic Acid ◽  
Brain Lesions ◽  
Significant Finding ◽  
Periodic Acid Schiff ◽  
Worldwide Distribution ◽  
Type D ◽  
Cerebellar Peduncles ◽  
Cerebral Microangiopathy ◽  
The Brain

Enterotoxemia caused by Clostridium perfringens type D is an important disease of sheep and goats with a worldwide distribution. Cerebral microangiopathy is considered pathognomonic for ovine enterotoxemia and is seen in most cases of the disorder in sheep. However, these lesions are poorly described in goats. In this article, we describe the vasculocentric brain lesions in 44 cases of caprine spontaneous C. perfringens type D enterotoxemia. Only 1 goat had gross changes in the brain, which consisted of mild cerebellar coning. However, 8 of 44 (18%) cases showed microscopic brain lesions, characterized by intramural vascular proteinaceous edema, a novel and diagnostically significant finding. The precise location of the edema was better observed with periodic acid–Schiff, Gomori’s, and albumin stains. Glial fibrillary acidic protein and aquaporin 4 immunostaining revealed strong immunolabeling of astrocyte foot processes surrounding microvessels. The areas of the brain most frequently affected were the cerebral cortex, corpus striatum (basal ganglia), and cerebellar peduncles, and both arterioles and venules were involved. Most of the goats of this study showed lesions in the intestine (enteritis, colitis, and typhlitis), although pulmonary congestion and edema, hydrothorax, hydropericardium, and ascites were also described. Although the intramural edema described, for the first time, in these caprine cases is useful for the diagnosis of enterotoxemia when observed, its absence cannot exclude the disease.

scholarly journals Genomic Analysis of Clostridium perfringens BEC/CPILE-Positive, Toxinotype D and E Strains Isolated from Healthy Children

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 543
Author(s):  
Raymond Kiu ◽  
Kathleen Sim ◽  
Alex Shaw ◽  
Emma Cornwell ◽  
Derek Pickard ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Genomic Analysis ◽  
Future Research ◽  
Toxin Gene ◽  
Healthy Children ◽  
Healthy Individuals ◽  
Type D ◽  
Plasmid Analysis ◽  
Putative Toxin ◽  
Specific Trait

Clostridium perfringens toxinotype D, toxinotype E, and gastroenteritis-linked BEC/CPILE-positive strains have never been reported in healthy children. We isolated, whole-genome sequenced and bioinformatically characterised three C. perfringens isolates—type D (IQ1), type E (IQ2) and BEC/CPILE-positive (IQ3), recovered from the stools of three healthy two-year-olds, which were further compared to 128 C. perfringens genomes available from NCBI. The analysis uncovered a previously under-described putative toxin gene alv (alveolysin) encoded by isolates IQ2 and IQ3, which appeared to be a clade-specific trait associated with strains from domestic animals. A plasmid analysis indicated that the iota-toxin was encoded on a near-intact previously described plasmid pCPPB-1 in type E strain IQ2. The BEC genes becA and becB were carried on a near-identical pCPOS-1 plasmid previously associated with Japanese gastroenteritis outbreaks. Furthermore, a close phylogenetic relatedness was inferred between the French C. perfringens type E isolates cp515.17 and newly sequenced IQ2, suggesting geographical links. This study describes novel C. perfringens isolates from healthy individuals which encode important toxin genes, indicating the potential spread of these veterinary and clinically important strains and mobile genetic elements, and highlights areas for future research.

scholarly journals Outbreak of Clostridium perfringens type D enterotoxemia in sheep

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.

scholarly journals Pathogenesis and diagnostic features of brain and ophthalmic damage produced by Clostridium perfringens type D epsilon toxin

2020 ◽  
Vol 32 (2) ◽  
pp. 282-286 ◽  
Author(s):  
John W. Finnie ◽  
Mauricio A. Navarro ◽  
Francisco A. Uzal
Keyword(s):  
Clostridium Perfringens ◽  
Vasogenic Edema ◽  
Differential Susceptibility ◽  
Brain Regions ◽  
Cerebral Lesions ◽  
Diagnostic Features ◽  
Microvascular Damage ◽  
Neurologic Disorder ◽  
Type D ◽  
Epsilon Toxin

Clostridium perfringens type D epsilon toxin (EXT) causes an important neurologic disorder of sheep, goats and, rarely, cattle. The disease can occur in peracute, acute, subacute, and chronic forms. High circulating levels of ETX produce vasculocentric brain lesions, in which microvascular endothelial injury results in diagnostically useful perivascular and intramural extravasations of plasma protein, especially in sheep, and less frequently in goats. With lower toxin doses, a more protracted clinical course tends to occur, particularly in sheep, leading to focal, bilaterally symmetrical, necrotic foci in certain brain regions. Although these morphologic features usually permit the diagnostic pathologist to make a definitive etiologic diagnosis, there are many aspects of the pathogenesis of these cerebral lesions that are not completely understood. ETX has also been shown to produce microvascular damage in the retina of rats, resulting in severe, diffuse vasogenic edema, similar to that found in brains exposed to this neurotoxin. The pathoclisis and vascular theories offer alternative explanations of the differential susceptibility of different brain regions to the same neurotoxic insult.

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