The comparative pathology of Clostridium difficile-associated disease

Michael K Keel, J. G. Songer

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Clostridium difficile is a confirmed pathogen in a wide variety of mammals, but the incidence of disease varies greatly in relation to host species, age, environmental density of spores, administration of antibiotics, and possibly, other factors. Lesions vary as well, in severity and distribution within individuals, and in some instances, age groups, of a given species. The cecum and colon are principally affected in most species, but foals and rabbits develop severe jejunal lesions. Explanations for variable susceptibility of species, and age groups within a species, are largely speculative. Differences in colonization rates and toxin-receptor densities have been proposed. Clostridium difficile-associated disease is most commonly diagnosed in Syrian hamsters, horses, and neonatal pigs, but it is reported sporadically in many other species. The essential virulence factors of C. difficile are large exotoxins, toxin A (TcdA) and toxin B (TcdB). Receptor-mediated endocytosis of the toxins is followed by endosomal acidification, a necessary step for conversion of the toxin to its active form in the cytosol. Cell-surface receptors have been characterized for TcdA, but remain to be identified for TcdB. Both TcdA and TcdB disrupt the actin cytoskeleton by disrupting Rho-subtype, intracellular signaling molecules. Disruption of the actin cytoskeleton is catastrophic for cellular function, but inflammation and neurogenic stimuli are also involved in the pathogenesis of the disease.

Original languageEnglish (US)
Pages (from-to)225-240
Number of pages16
JournalVeterinary Pathology
Volume43
Issue number3
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

Clostridium difficile
toxins
Pathology
Actin Cytoskeleton
Age Groups
Neurogenic Inflammation
Exotoxins
Cecum
Mesocricetus
Cell Surface Receptors
Virulence Factors
Endocytosis
Spores
Cytosol
Horses
microfilaments
Mammals
lesions (animal)
Colon
Swine

Keywords

  • Antibiotic-associated diarrhea
  • Clostridium difficile
  • Colitis
  • Enteritis
  • Exotoxin
  • TcdA
  • TcdB
  • Typhlocolitis

ASJC Scopus subject areas

  • veterinary(all)

Cite this

The comparative pathology of Clostridium difficile-associated disease. / Keel, Michael K; Songer, J. G.

In: Veterinary Pathology, Vol. 43, No. 3, 05.2006, p. 225-240.

Research output: Contribution to journalArticle

@article{947a422954d040f2b9a4240d81b4cc27,
title = "The comparative pathology of Clostridium difficile-associated disease",
abstract = "Clostridium difficile is a confirmed pathogen in a wide variety of mammals, but the incidence of disease varies greatly in relation to host species, age, environmental density of spores, administration of antibiotics, and possibly, other factors. Lesions vary as well, in severity and distribution within individuals, and in some instances, age groups, of a given species. The cecum and colon are principally affected in most species, but foals and rabbits develop severe jejunal lesions. Explanations for variable susceptibility of species, and age groups within a species, are largely speculative. Differences in colonization rates and toxin-receptor densities have been proposed. Clostridium difficile-associated disease is most commonly diagnosed in Syrian hamsters, horses, and neonatal pigs, but it is reported sporadically in many other species. The essential virulence factors of C. difficile are large exotoxins, toxin A (TcdA) and toxin B (TcdB). Receptor-mediated endocytosis of the toxins is followed by endosomal acidification, a necessary step for conversion of the toxin to its active form in the cytosol. Cell-surface receptors have been characterized for TcdA, but remain to be identified for TcdB. Both TcdA and TcdB disrupt the actin cytoskeleton by disrupting Rho-subtype, intracellular signaling molecules. Disruption of the actin cytoskeleton is catastrophic for cellular function, but inflammation and neurogenic stimuli are also involved in the pathogenesis of the disease.",
keywords = "Antibiotic-associated diarrhea, Clostridium difficile, Colitis, Enteritis, Exotoxin, TcdA, TcdB, Typhlocolitis",
author = "Keel, {Michael K} and Songer, {J. G.}",
year = "2006",
month = "5",
doi = "10.1354/vp.43-3-225",
language = "English (US)",
volume = "43",
pages = "225--240",
journal = "Veterinary Pathology",
issn = "0300-9858",
publisher = "SAGE Publications Ltd",
number = "3",

}

TY - JOUR

T1 - The comparative pathology of Clostridium difficile-associated disease

AU - Keel, Michael K

AU - Songer, J. G.

PY - 2006/5

Y1 - 2006/5

N2 - Clostridium difficile is a confirmed pathogen in a wide variety of mammals, but the incidence of disease varies greatly in relation to host species, age, environmental density of spores, administration of antibiotics, and possibly, other factors. Lesions vary as well, in severity and distribution within individuals, and in some instances, age groups, of a given species. The cecum and colon are principally affected in most species, but foals and rabbits develop severe jejunal lesions. Explanations for variable susceptibility of species, and age groups within a species, are largely speculative. Differences in colonization rates and toxin-receptor densities have been proposed. Clostridium difficile-associated disease is most commonly diagnosed in Syrian hamsters, horses, and neonatal pigs, but it is reported sporadically in many other species. The essential virulence factors of C. difficile are large exotoxins, toxin A (TcdA) and toxin B (TcdB). Receptor-mediated endocytosis of the toxins is followed by endosomal acidification, a necessary step for conversion of the toxin to its active form in the cytosol. Cell-surface receptors have been characterized for TcdA, but remain to be identified for TcdB. Both TcdA and TcdB disrupt the actin cytoskeleton by disrupting Rho-subtype, intracellular signaling molecules. Disruption of the actin cytoskeleton is catastrophic for cellular function, but inflammation and neurogenic stimuli are also involved in the pathogenesis of the disease.

AB - Clostridium difficile is a confirmed pathogen in a wide variety of mammals, but the incidence of disease varies greatly in relation to host species, age, environmental density of spores, administration of antibiotics, and possibly, other factors. Lesions vary as well, in severity and distribution within individuals, and in some instances, age groups, of a given species. The cecum and colon are principally affected in most species, but foals and rabbits develop severe jejunal lesions. Explanations for variable susceptibility of species, and age groups within a species, are largely speculative. Differences in colonization rates and toxin-receptor densities have been proposed. Clostridium difficile-associated disease is most commonly diagnosed in Syrian hamsters, horses, and neonatal pigs, but it is reported sporadically in many other species. The essential virulence factors of C. difficile are large exotoxins, toxin A (TcdA) and toxin B (TcdB). Receptor-mediated endocytosis of the toxins is followed by endosomal acidification, a necessary step for conversion of the toxin to its active form in the cytosol. Cell-surface receptors have been characterized for TcdA, but remain to be identified for TcdB. Both TcdA and TcdB disrupt the actin cytoskeleton by disrupting Rho-subtype, intracellular signaling molecules. Disruption of the actin cytoskeleton is catastrophic for cellular function, but inflammation and neurogenic stimuli are also involved in the pathogenesis of the disease.

KW - Antibiotic-associated diarrhea

KW - Clostridium difficile

KW - Colitis

KW - Enteritis

KW - Exotoxin

KW - TcdA

KW - TcdB

KW - Typhlocolitis

UR - http://www.scopus.com/inward/record.url?scp=33646439545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646439545&partnerID=8YFLogxK

U2 - 10.1354/vp.43-3-225

DO - 10.1354/vp.43-3-225

M3 - Article

VL - 43

SP - 225

EP - 240

JO - Veterinary Pathology

JF - Veterinary Pathology

SN - 0300-9858

IS - 3

ER -