The role of enterotoxin in Clostridium perfringens type A enteritis

1971 ◽  
Vol 17 (7) ◽  
pp. 987-991 ◽  
Author(s):  
A. H. W. Hauschild ◽  
L. Niilo ◽  
W. J. Dorward

Vegetative cells of three strains of Clostridium perfringens type A, free of erythemal activity, were suspended in fresh medium and injected into ligated intestinal loops of lambs. Examination of the loop contents after 6.5 h showed significant accumulation of fluid, multiplication and sporulation of C. perfringens, and erythemal activity in both the supernatant fluids and the sediments.The erythemal factor produced in vivo was identical with the erythemal factor of sporulated cells of C. perfringens grown in vitro, and again caused accumulation of fluid when transferred into ligated intestinal loops of recipient lambs. Immune rabbit serum prepared against extracts from sporulated cells of C. perfringens, and absorbed with extracts from vegetative cells of the same strain, completely neutralized the enterotoxic and erythemal activities of the in vivo-produced factor.It is concluded that the erythemal factor is the causative agent in C. perfringens type A enteritis. The term "Clostridium perfringens enterotoxin" is proposed to characterize the erythemal factor.

1975 ◽  
Vol 21 (4) ◽  
pp. 521-527 ◽  
Author(s):  
Noritake Asato ◽  
Maria van Soestbergen ◽  
F William Sunderman

Abstract Binding of 63Ni(Il) to ultrafiltrable constituents of rabbit serum was studied (a) after in vitro incubation (2 h, 37 °C) of rabbit serum with 63NiCl2 (10-100 µmol/liter), and (b) at intervals (0.25-2 h) after in vivo administration of 63NiCl2 (40-160 µmol/kg body wt, i.v.). Serum ultrafiltrates were fractionated by thin-layer chromatography, and the separated compounds made visible by autoradiography and by ninhydrin staining. Several (≃5) ultrafiltrable 63Ni-complexes were demonstrable as distinct radiodense 63Ni-bands with chromatographic mobilities corresponding to those of ninhydrin-positive bands. Unbound 63Ni(II) was not detected in serum ultrafiltrates in either the in vitro or in vivo experiments. In sera (n = 10) incubated in vitro with 63Ni(II) (10 µmol/ liter), the mean percentage of ultrafiltrable 63Ni was 36% (range = 33-38) of total serum 63Ni. In contrast, in sera (n = 10) obtained 2 h after i.v. injection of 63Ni(II) (40 µmol/kg), the mean concentration of total serum 63Ni was 10.8 µmol/liter (range = 6-14), and the mean percentage of ultrafiltrable 63Ni was 15% (range = 9-21) of total serum 63Ni. The disparity between the percentages of ultrafiltrable 63Ni obtained in vitro and in vivo was obviated when the in vivo experiments were performed in rabbits bilaterally nephrectomized, with ligated common bile ducts. This investigation confirms the existence of several nickel receptors in serum ultrafiltrates and substantiates the role of ultrafiltrable complexes in the excretion of nickel.


Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 893
Author(s):  
Basma Tarek ◽  
Julia Bruggisser ◽  
Filippo Cattalani ◽  
Horst Posthaus

Beta toxin (CPB) is a small hemolysin beta pore-forming toxin (β-PFT) produced by Clostridium perfringens type C. It plays a central role in the pathogenesis of necro-hemorrhagic enteritis in young animals and humans via targeting intestinal endothelial cells. We recently identified the membrane protein CD31 (PECAM-1) as the receptor for CPB on mouse endothelial cells. We now assess the role of CD31 in CPB cytotoxicity against human endothelial and monocytic cells using a CRISPR/Cas9 gene knockout and an antibody blocking approach. CD31 knockout human endothelial and monocytic cells were resistant to CPB and CPB oligomers only formed in CD31-expressing cells. CD31 knockout endothelial and monocytic cells could be selectively enriched out of a polyclonal cell population by exposing them to CPB. Moreover, antibody mediated blocking of the extracellular Ig6 domain of CD31 abolished CPB cytotoxicity and oligomer formation in endothelial and monocytic cells. In conclusion, this study confirms the role of CD31 as a receptor of CPB on human endothelial and monocytic cells. Specific interaction with the CD31 molecule can thus explain the cell type specificity of CPB observed in vitro and corresponds to in vivo observations in naturally diseased animals.


1983 ◽  
Vol 46 (12) ◽  
pp. 1069-1073 ◽  
Author(s):  
GERARD N. STELMA ◽  
JOHN C. WIMSATT ◽  
PETER E. KAUFFMAN ◽  
DHIRENDRA B. SHAH

Fourteen isolates of Clostridium perfringens obtained from food-poisoning outbreaks were screened for enterotoxigenicity using a radioimmunoassay (RIA) that detects 1.0 ng of enterotoxin/ml. Only four of the isolates produced enterotoxin in concentrations too low to be detected by counterimmunoelectrophoresis when grown in Duncan-Strong sporulation (D-S) medium. Substitution of raffinose for soluble starch or addition of theobromine to the medium stimulated enterotoxin production by three of the four enterotoxin-positive isolates. Raffinose and theobromine did not stimulate enterotoxin production by isolates that were enterotoxin-negative in D-S medium. Enterotoxin production by the RIA-positive strains correlated with the numbers of heat-resistant spores they produced. The RIA-negative isolates produced approximately the same numbers of spores/ml as the high enterotoxin producers, and more spores/ml than strain H8 produced under optimum conditions. Therefore, inability to sporulate is not the cause for failure of these isolates to produce enterotoxin. Rabbit ileal loop assays showed that the two isolates that were lowest enterotoxin producers in vitro were highly active in vivo.


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4393
Author(s):  
Jessica Pahle ◽  
Dennis Kobelt ◽  
Jutta Aumann ◽  
Diana Behrens ◽  
Ole Daberkow ◽  
...  

Pancreatic cancer (PC) is one of the most lethal cancers worldwide, associated with poor prognosis and restricted therapeutic options. Clostridium perfringens enterotoxin (CPE), is a pore-forming (oncoleaking) toxin, which binds to claudin-3 and -4 (Cldn3/4) causing selective cytotoxicity. Cldn3/4 are highly upregulated in PC and represent an effective target for oncoleaking therapy. We utilized a translation-optimized CPE vector (optCPE) for new suicide approach of PC in vitro and in cell lines (CDX) and patient-derived pancreatic cancer xenografts (PDX) in vivo. The study demonstrates selective toxicity in Cldn3/4 overexpressing PC cells by optCPE gene transfer, mediated by pore formation, activation of apoptotic/necrotic signaling in vitro, induction of necrosis and of bystander tumor cell killing in vivo. The optCPE non-viral intratumoral in vivo jet-injection gene therapy shows targeted antitumoral efficacy in different CDX and PDX PC models, leading to reduced tumor viability and induction of tumor necrosis, which is further enhanced if combined with chemotherapy. This selective oncoleaking suicide gene therapy improves therapeutic efficacy in pancreas carcinoma and will be of value for better local control, particularly of unresectable or therapy refractory PC.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.


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