Lesion Development in a New Intestinal Loop Model Indicates the Involvement of a Shared Clostridium perfringens Virulence Factor in Haemorrhagic Enteritis in Calves

2013 ◽  
Vol 149 (1) ◽  
pp. 103-112 ◽  
Author(s):  
B. Valgaeren ◽  
B. Pardon ◽  
E. Goossens ◽  
S. Verherstraeten ◽  
S. Schauvliege ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Virulence Factor ◽  
Intestinal Loop ◽  
Loop Model ◽  
Lesion Development

scholarly journals Toxin-neutralizing antibodies protect against Clostridium perfringens-induced necrosis in an intestinal loop model for bovine necrohemorrhagic enteritis

2016 ◽  
Vol 12 (1) ◽  
Author(s):  
Evy Goossens ◽  
Stefanie Verherstraeten ◽  
Bonnie R. Valgaeren ◽  
Bart Pardon ◽  
Leen Timbermont ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Neutralizing Antibodies ◽  
Intestinal Loop ◽  
Loop Model

scholarly journals Development and Application of a Mouse Intestinal Loop Model To Study theIn VivoAction of Clostridium perfringens Enterotoxin

2011 ◽  
Vol 79 (8) ◽  
pp. 3020-3027 ◽  
Author(s):  
Justin A. Caserta ◽  
Susan L. Robertson ◽  
Juliann Saputo ◽  
Archana Shrestha ◽  
Bruce A. McClane ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Cell Damage ◽  
Gastrointestinal Symptoms ◽  
Food Poisoning ◽  
The United States ◽  
Intestinal Lumen ◽  
Intestinal Loop ◽  
Loop Model ◽  
Internal Organs ◽  
Content Type

ABSTRACTClostridium perfringensenterotoxin (CPE) is responsible for causing the gastrointestinal symptoms ofC. perfringenstype A food poisoning, the second most commonly identified bacterial food-borne illness in the United States. CPE is produced by sporulatingC. perfringenscells in the small intestinal lumen, where it then causes epithelial cell damage and villous blunting that leads to diarrhea and cramping. Those effects are typically self-limiting; however, severe outbreaks of this food poisoning, particularly two occurring in psychiatric institutions, have involved deaths. Since animal models are currently limited for the study of the CPE action, a mouse ligated intestinal loop model was developed. With this model, significant lethality was observed after 2 h in loops receiving an inoculum of 100 or 200 μg of CPE but not using a 50-μg toxin inoculum. A correlation was noted between the overall intestinal histological damage and lethality in mice. Serum analysis revealed a dose-dependent increase in serum CPE and potassium levels. CPE binding to the liver and kidney was detected, along with elevated levels of potassium in the serum. These data suggest that CPE can be absorbed from the intestine into the circulation, followed by the binding of the toxin to internal organs to induce potassium leakage, which can cause death. Finally, CPE pore complexes similar to those formed in tissue culture cells were detected in the intestine and liver, suggesting that (i) CPE actions are similarin vivoandin vitroand (ii) CPE-induced potassium release into blood may result from CPE pore formation in internal organs such as the liver.

scholarly journals Effects of Clostridium perfringens Beta-Toxin on the Rabbit Small Intestine and Colon

2008 ◽  
Vol 76 (10) ◽  
pp. 4396-4404 ◽  
Author(s):  
Jorge E. Vidal ◽  
Bruce A. McClane ◽  
Juliann Saputo ◽  
Jaquelyn Parker ◽  
Francisco A. Uzal
Keyword(s):  
Small Intestine ◽  
Clostridium Perfringens ◽  
Time Course ◽  
Defense Mechanism ◽  
Intestinal Damage ◽  
Loop Model ◽  
Type B ◽  
Ileal Loop ◽  
Type C ◽  
Beta Toxin

ABSTRACT Clostridium perfringens type B and type C isolates, which produce beta-toxin (CPB), cause fatal diseases originating in the intestines of humans or livestock. Our previous studies demonstrated that CPB is necessary for type C isolate CN3685 to cause bloody necrotic enteritis in a rabbit ileal loop model and also showed that purified CPB, in the presence of trypsin inhibitor (TI), can reproduce type C pathology in rabbit ileal loops. We report here a more complete characterization of the effects of purified CPB in the rabbit small and large intestines. One microgram of purified CPB, in the presence of TI, was found to be sufficient to cause significant accumulation of hemorrhagic luminal fluid in duodenal, jejunal, or ileal loops treated for 6 h with purified CPB, while no damage was observed in corresponding loops receiving CPB (no TI) or TI alone. In contrast to the CPB sensitivity of the small intestine, the colon was not affected by 6 h of treatment with even 90 μg of purified CPB whether or not TI was present. Time course studies showed that purified CPB begins to induce small intestinal damage within 1 h, at which time the duodenum is less damaged than the jejunum or ileum. These observations help to explain why type B and C infections primarily involve the small intestine, establish CPB as a very potent and fast-acting toxin in the small intestines, and confirm a key role for intestinal trypsin as an innate intestinal defense mechanism against CPB-producing C. perfringens isolates.

scholarly journals Multi-Omics Approach Reveals the Potential Core Vaccine Targets for the Emerging Foodborne Pathogen Campylobacter jejuni

2021 ◽  
Vol 12 ◽  
Author(s):  
Hengchun Cao ◽  
Hanxiao Xu ◽  
Chunhui Ning ◽  
Li Xiang ◽  
Qiufang Ren ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Virulence Factor ◽  
Target Genes ◽  
Bacterial Resistance ◽  
Animal Experiments ◽  
Foodborne Pathogen ◽  
Gene Families ◽  
Intestinal Loop ◽  
Potential Core ◽  
New Vaccines

Campylobacter jejuni is a leading cause of bacterial gastroenteritis in humans around the world. The emergence of bacterial resistance is becoming more serious; therefore, development of new vaccines is considered to be an alternative strategy against drug-resistant pathogen. In this study, we investigated the pangenome of 173 C. jejuni strains and analyzed the phylogenesis and the virulence factor genes. In order to acquire a high-quality pangenome, genomic relatedness was firstly performed with average nucleotide identity (ANI) analyses, and an open pangenome of 8,041 gene families was obtained with the correct taxonomy genomes. Subsequently, the virulence property of the core genome was analyzed and 145 core virulence factor (VF) genes were obtained. Upon functional genomics and immunological analyses, five core VF proteins with high antigenicity were selected as potential core vaccine targets for humans. Furthermore, functional annotations indicated that these proteins are involved in important molecular functions and biological processes, such as adhesion, regulation, and secretion. In addition, transcriptome analysis in human cells and pig intestinal loop proved that these vaccine target genes are important in the virulence of C. jejuni in different hosts. Comprehensive pangenome and relevant animal experiments will facilitate discovering the potential core vaccine targets with improved efficiency in reverse vaccinology. Likewise, this study provided some insights into the genetic polymorphism and phylogeny of C. jejuni and discovered potential vaccine candidates for humans. Prospective development of new vaccines using the targets will be an alternative to the use of antibiotics and prevent the development of multidrug-resistant C. jejuni in humans and even other animals.

scholarly journals Toxin B Variants from Clostridium difficile Strains VPI 10463 and NAP1/027 Share Similar Substrate Profile and Cellular Intoxication Kinetics but Use Different Host Cell Entry Factors

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 348 ◽  
Author(s):  
Diana López-Ureña ◽  
Josué Orozco-Aguilar ◽  
Yendry Chaves-Madrigal ◽  
Andrea Ramírez-Mata ◽  
Amanda Villalobos-Jimenez ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Small Gtpases ◽  
Cell Entry ◽  
Intestinal Loop ◽  
Loop Model ◽  
Toxin B ◽  
Binding Domains ◽  
Crucial Difference ◽  
Sequence Variations

Clostridium difficile induces antibiotic-associated diarrhea due to the release of toxin A (TcdA) and toxin B (TcdB), the latter being its main virulence factor. The epidemic strain NAP1/027 has an increased virulence attributed to different factors. We compared cellular intoxication by TcdBNAP1 with that by the reference strain VPI 10463 (TcdBVPI). In a mouse ligated intestinal loop model, TcdBNAP1 induced higher neutrophil recruitment, cytokine release, and epithelial damage than TcdBVPI. Both toxins modified the same panel of small GTPases and exhibited similar in vitro autoprocessing kinetics. On the basis of sequence variations in the frizzled-binding domain (FBD), we reasoned that TcdBVPI and TcdBNAP1 might have different receptor specificities. To test this possibility, we used a TcdB from a NAP1 variant strain (TcdBNAP1v) unable to glucosylate RhoA but with the same receptor-binding domains as TcdBNAP1. Cells were preincubated with TcdBNAP1v to block cellular receptors, prior to intoxication with either TcdBVPI or TcdBNAP1. Preincubation with TcdBNAP1v blocked RhoA glucosylation by TcdBNAP1 but not by TcdBVPI, indicating that the toxins use different host factors for cell entry. This crucial difference might explain the increased biological activity of TcdBNAP1 in the intestine, representing a contributing factor for the increased virulence of the NAP1/027 strain.

scholarly journals Application of a pig ligated intestinal loop model for early Lawsonia intracellularis infection

2010 ◽  
Vol 52 (1) ◽  
pp. 17 ◽  
Author(s):  
Torsten S Boutrup ◽  
Kirsten Schauser ◽  
Jørgen S Agerholm ◽  
Tim K Jensen
Keyword(s):  
Intestinal Loop ◽  
Loop Model ◽  
Lawsonia Intracellularis

scholarly journals A role for stem cell factor and c-kit in the murine intestinal tract secretory response to cholera toxin.

1995 ◽  
Vol 182 (6) ◽  
pp. 1931-1942 ◽  
Author(s):  
G R Klimpel ◽  
A K Chopra ◽  
K E Langley ◽  
J Wypych ◽  
C A Annable ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cholera Toxin ◽  
Stem Cell Factor ◽  
Intestinal Tract ◽  
Secretory Response ◽  
Histological Evaluation ◽  
Epithelial Cell Line ◽  
Intestinal Loop ◽  
Loop Model

The role of stem cell factor (SCF) and its receptor (c-kit) in the intestinal secretory response to cholera toxin (CT) was investigated using a ligated intestinal loop model in mice having mutations in the dominant white spotting (W) locus and the steel (Sl) locus. W/Wv mice, which express an aberrant form of the c-kit protein, failed to give an intestinal secretory response after luminal CT challenge. In contrast, W/Wv mice and their control littermates had equivalent intestinal secretory responses to Escherichia coli heat-stable enterotoxin (STa). Sl/Sld mice, which express only a soluble truncated form of SCF, also gave a significantly reduced intestinal secretory response to CT when compared to the secretory response of their littermate controls. The unresponsiveness of W/Wv mice to CT was restricted to the intestinal tract since these mice had foot pad swelling responses to CT challenge that were equivalent to their littermate controls. Restoration of mast cells in W/Wv mice by bone marrow transplantation of control littermate bone marrow did not reverse the CT-unresponsiveness of the intestinal tract. Histological evaluation of the gastrointestinal tract from W/Wv mice showed a normal distribution of enterochromaffin cells (ECC). CT challenge of either ligated intestinal loops from C57B1/6 mice or a mouse intestinal epithelial cell line (MODE-K) resulted in elevated levels of mRNA for SCF. MODE-K cells exposed to CT also had enhanced expression of c-kit. Finally, fluid obtained from CT-challenged ligated intestinal loops from C57B1/6 mice contained significant levels of SCF. Taken together, the above results suggest that CT-induced intestinal secretory responses are dependent upon SCF-c-kit interactions. These interactions appear to be induced as a consequence of CT stimulation of the intestinal tract and may also play a role in the development or functionality of the enteric nervous system.

Immunization of sheep against experimental Clostridium perfringens type A enteritis

1971 ◽  
Vol 17 (3) ◽  
pp. 391-395 ◽  
Author(s):  
L. Niilo ◽  
A. H. W. Hauschild ◽  
W. J. Dorward
Keyword(s):  
Clostridium Perfringens ◽  
Protective Immunity ◽  
Type A ◽  
Cell Extract ◽  
Intestinal Loop ◽  
Whole Cells ◽  
Enteropathogenic Strain ◽  
Specific Band

Lambs were injected parenterally with formalized cell extract, or bacterin, prepared from sporulating cultures of an enteropathogenic strain of Clostridium perfringens type A. This procedure induced an antibody in the serum which neutralized the erythemal and enteropathogenic activities of the cell extract. Immunodiffusion of the serum against the toxic cell extract produced a single, specific band associated with enteropathogenic activity. Protective immunity was not evident when the immunized lambs were challenged by the intraduodenal and the ligated intestinal loop methods with toxic cell extract or with whole cells of C. perfringens. Non-immunized lambs, challenged nine times by the intraduodenal method over a period of 70 days, had no measurable antibody and remained susceptible to experimental enteritis.

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