English
French
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.
Publication Date: 2006-05-05 PubMed ID: 16672570DOI: 10.1354/vp.43-3-225Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Review
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research paper delves into the pathology of disease associated with Clostridium difficile, a pathogen found in various mammals. The authors explore how this disease varies across different species, the significance of certain factors, and the differences in toxin-receptors found in different host species.
Examining different host species
- The authors point out that Clostridium difficile is a proven pathogen in a vast array of animals, including but not restricted to Syrian hamsters, horses, and newborn pigs. However, there’s a significant variability in the disease incidence that depends on the host species, its age, environmental spore density, use of antibiotics, and perhaps other yet unknown factors.
- The researchers further state that lesion severity and distribution can also vary within individuals and across age groups of a specific species.
Focusing on cecum and colon
- Most of the species principally get affected in the cecum and colon. However, foals and rabbits develop extreme lesions in the jejunum. The reason for different susceptibility in species, and age groups within a species, remains mostly hypothetical at this stage.
Understanding the role of toxins and receptors
- As per the research, variations in colonization rates and the density of toxin-receptors are put forth as possible explanations for the varying incidence of the disease.
- It is established that the essential virulence factors of C. difficile are exotoxins, specifically toxin A (TcdA) and toxin B (TcdB). These toxins gain entry into the cell via receptor-mediated endocytosis, which is then followed by endosomal acidification – a needed step for converting the toxin to its active form within the cytosol.
- While cell-surface receptors for TcdA have been characterized, those for TcdB are yet to be identified. Both TcdA and TcdB can cause havoc to cellular function by disrupting the actin cytoskeleton – crucial intracellular signaling molecules.
Implications of the disease
- This disruption of the actin cytoskeleton is said to have catastrophic effects on cellular function. The paper also mentions inflammation and neurogenic stimuli as parts of the disease process.
Cite This Article
APA
Keel MK, Songer JG.
(2006).
The comparative pathology of Clostridium difficile-associated disease.
Vet Pathol, 43(3), 225-240.
https://doi.org/10.1354/vp.43-3-225 Publication
Researcher Affiliations
- The University of Arizona, Department of Veterinary Sciences and Microbiology, Building #90, Room 212, 1117 East Lowell St., Tucson, AZ 85721, USA.
MeSH Terms
- Animal Diseases / epidemiology
- Animal Diseases / microbiology
- Animal Diseases / pathology
- Animals
- Clostridioides difficile / pathogenicity
- Disease Susceptibility
- Enterocolitis, Pseudomembranous / epidemiology
- Enterocolitis, Pseudomembranous / microbiology
- Enterocolitis, Pseudomembranous / pathology
- Enterocolitis, Pseudomembranous / veterinary
- Intestines / pathology
Citations
This article has been cited 49 times.- Lu00fchrmann A, Palmini A, Hellmich J, Belik V, Zentek J, Vahjen W. Antimicrobial resistance- and pathogen patterns in the fecal microbiota of sows and their offspring in German commercial pig farms.. PLoS One 2023;18(8):e0290554.
- Hain-Saunders NMR, Knight DR, Bruce M, Byrne D, Riley TV. Genomic Analysis of Clostridioides difficile Recovered from Horses in Western Australia.. Microorganisms 2023 Jul 3;11(7).
- Tsekouras N, Meletis E, Kostoulas P, Labronikou G, Athanasakopoulou Z, Christodoulopoulos G, Billinis C, Papatsiros VG. Detection of Enterotoxigenic Escherichia coli and Clostridia in the Aetiology of Neonatal Piglet Diarrhoea: Important Factors for Their Prevention.. Life (Basel) 2023 Apr 27;13(5).
- Cheng JKJ, Unnikrishnan M. Clostridioides difficile infection: traversing host-pathogen interactions in the gut.. Microbiology (Reading) 2023 Feb;169(2).
- Diniz AN, Moura LNF, Cruz DSG, Oliveira Junior CA, Figueiredo HCP, Cunha JLR, Vilela EG, Kuijper EJ, Wilcox MH, Lobato FCF, Silva ROS. Characterization of the virulence of three novel clade 2 Clostridioides (Clostridium) difficile strains and a two-year screening in animals and humans in Brazil.. PLoS One 2022;17(8):e0273013.
- Uzal FA, Navarro MA, Asin J, Henderson EE. Clostridial Diseases of Horses: A Review.. Vaccines (Basel) 2022 Feb 17;10(2).
- Hain-Saunders NMR, Knight DR, Bruce M, Riley TV. Clostridioides difficile infection and One Health: an equine perspective.. Environ Microbiol 2022 Mar;24(3):985-997.
- Uzal FA, Arroyo LG, Navarro MA, Gomez DE, Asu00edn J, Henderson E. Bacterial and viral enterocolitis in horses: a review.. J Vet Diagn Invest 2022 May;34(3):354-375.
- Proctor A, Cornick NA, Wang C, Mooyottu S, Arruda PA, Kobs K, Phillips GJ. Neonatal Piglets Are Protected from Clostridioides difficile Infection by Age-Dependent Increase in Intestinal Microbial Diversity.. Microbiol Spectr 2021 Oct 31;9(2):e0124321.
- Lu00fchrmann A, Ovadenko K, Hellmich J, Sudendey C, Belik V, Zentek J, Vahjen W. Characterization of the fecal microbiota of sows and their offspring from German commercial pig farms.. PLoS One 2021;16(8):e0256112.
- Horrigan O, Jose S, Mukherjee A, Sharma D, Huber A, Madan R. Leptin Receptor q223r Polymorphism Influences Clostridioides difficile Infection-Induced Neutrophil CXCR2 Expression in an Interleukin-1u03b2 Dependent Manner.. Front Cell Infect Microbiol 2021;11:619192.
- Emele MF, Joppe FM, Riedel T, Overmann J, Rupnik M, Cooper P, Kusumawati RL, Berger FK, Laukien F, Zimmermann O, Bohne W, Grou00df U, Bader O, Zautner AE. Proteotyping of Clostridioides difficile as Alternate Typing Method to Ribotyping Is Able to Distinguish the Ribotypes RT027 and RT176 From Other Ribotypes.. Front Microbiol 2019;10:2087.
- Watanabe TTN, Dubovi EJ, Evans DE, Langohr IM, Ferracone J, Ezelle LB, Del Piero F. Outbreak of canine parvovirus 2b and Clostridium difficile infection in Asian small-clawed otters.. J Vet Diagn Invest 2020 Mar;32(2):226-229.
- Knight DR, Riley TV. Genomic Delineation of Zoonotic Origins of Clostridium difficile.. Front Public Health 2019;7:164.
- Grzeu015bkowiak u0141M, Pieper R, Huynh HA, Cutting SM, Vahjen W, Zentek J. Impact of early-life events on the susceptibility to Clostridium difficile colonisation and infection in the offspring of the pig.. Gut Microbes 2019;10(2):251-259.
- Woods EC, Edwards AN, Childress KO, Jones JB, McBride SM. The C. difficile clnRAB operon initiates adaptations to the host environment in response to LL-37.. PLoS Pathog 2018 Aug;14(8):e1007153.
- Uzal FA, Navarro MA, Li J, Freedman JC, Shrestha A, McClane BA. Comparative pathogenesis of enteric clostridial infections in humans and animals.. Anaerobe 2018 Oct;53:11-20.
- Schmautz C, Hillreiner M, Ballweg I, Pfaffl MW, Kliem H. Stimulated enrichment of Clostridium difficile specific IgA in mature cow's milk.. PLoS One 2018;13(4):e0195275.
- Qin J, Dai Y, Ma X, Wang Y, Gao Q, Lu H, Li T, Meng H, Liu Q, Li M. Nosocomial transmission of Clostridium difficile Genotype ST81 in a General Teaching Hospital in China traced by whole genome sequencing.. Sci Rep 2017 Aug 29;7(1):9627.
- Mooyottu S, Flock G, Upadhyay A, Upadhyaya I, Maas K, Venkitanarayanan K. Protective Effect of Carvacrol against Gut Dysbiosis and Clostridium difficile Associated Disease in a Mouse Model.. Front Microbiol 2017;8:625.
- Juffo GD, Bassuino DM, Gomes DC, Wurster F, Pissetti C, Pavarini SP, Driemeier D. Equine salmonellosis in southern Brazil.. Trop Anim Health Prod 2017 Mar;49(3):475-482.
- Dhillon HS, Johnson G, Shannon M, Greenwood C, Roberts D, Bustin S. Homogeneous and digital proximity ligation assays for the detection of Clostridium difficile toxins A and B.. Biomol Detect Quantif 2016 Dec;10:2-8.
- McElroy MC, Hill M, Moloney G, Mac Aogu00e1in M, McGettrick S, O'Doherty u00c1, Rogers TR. Typhlocolitis associated with Clostridium difficile ribotypes 078 and 110 in neonatal piglets from a commercial Irish pig herd.. Ir Vet J 2015;69:10.
- Warn P, Thommes P, Sattar A, Corbett D, Flattery A, Zhang Z, Black T, Hernandez LD, Therien AG. Disease Progression and Resolution in Rodent Models of Clostridium difficile Infection and Impact of Antitoxin Antibodies and Vancomycin.. Antimicrob Agents Chemother 2016 Nov;60(11):6471-6482.
- Uzal FA, Diab SS. Gastritis, Enteritis, and Colitis in Horses.. Vet Clin North Am Equine Pract 2015 Aug;31(2):337-58.
- Zhao S, Ghose-Paul C, Zhang K, Tzipori S, Sun X. Immune-based treatment and prevention of Clostridium difficile infection.. Hum Vaccin Immunother 2014;10(12):3522-30.
- Schneeberg A, Ehricht R, Slickers P, Baier V, Neubauer H, Zimmermann S, Rabold D, Lu00fcbke-Becker A, Seyboldt C. DNA microarray-based PCR ribotyping of Clostridium difficile.. J Clin Microbiol 2015 Feb;53(2):433-42.
- Knight DR, Squire MM, Riley TV. Nationwide surveillance study of Clostridium difficile in Australian neonatal pigs shows high prevalence and heterogeneity of PCR ribotypes.. Appl Environ Microbiol 2015 Jan;81(1):119-23.
- Sun X, Hirota SA. The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection.. Mol Immunol 2015 Feb;63(2):193-202.
- Mooyottu S, Kollanoor-Johny A, Flock G, Bouillaut L, Upadhyay A, Sonenshein AL, Venkitanarayanan K. Carvacrol and trans-cinnamaldehyde reduce Clostridium difficile toxin production and cytotoxicity in vitro.. Int J Mol Sci 2014 Mar 12;15(3):4415-30.
- Himsworth CG, Patrick DM, Mak S, Jardine CM, Tang P, Weese JS. Carriage of Clostridium difficile by wild urban Norway rats (Rattus norvegicus) and black rats (Rattus rattus).. Appl Environ Microbiol 2014 Feb;80(4):1299-305.
- Mackin KE, Carter GP, Howarth P, Rood JI, Lyras D. Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile.. PLoS One 2013;8(11):e79666.
- Silva RO, Santos RL, Pires PS, Pereira LC, Pereira ST, Duarte MC, de Assis RA, Lobato FC. Detection of toxins A/B and isolation of Clostridium difficile and Clostridium perfringens from dogs in Minas Gerais, Brazil.. Braz J Microbiol 2013;44(1):133-7.
- Kongsted H, Jonach B, Haugegaard S, Angen O, Jorsal SE, Kokotovic B, Larsen LE, Jensen TK, Nielsen JP. Microbiological, pathological and histological findings in four Danish pig herds affected by a new neonatal diarrhoea syndrome.. BMC Vet Res 2013 Oct 12;9:206.
- Schneeberg A, Neubauer H, Schmoock G, Baier S, Harlizius J, Nienhoff H, Brase K, Zimmermann S, Seyboldt C. Clostridium difficile genotypes in piglet populations in Germany.. J Clin Microbiol 2013 Nov;51(11):3796-803.
- Stiles BG, Wigelsworth DJ, Popoff MR, Barth H. Clostridial binary toxins: iota and C2 family portraits.. Front Cell Infect Microbiol 2011;1:11.
- Schoster A, Arroyo LG, Staempfli HR, Shewen PE, Weese JS. Presence and molecular characterization of Clostridium difficile and Clostridium perfringens in intestinal compartments of healthy horses.. BMC Vet Res 2012 Jun 29;8:94.
- Sun X, Savidge T, Feng H. The enterotoxicity of Clostridium difficile toxins.. Toxins (Basel) 2010 Jul;2(7):1848-80.
- Weese JS, Rousseau J, Deckert A, Gow S, Reid-Smith RJ. Clostridium difficile and methicillin-resistant Staphylococcus aureus shedding by slaughter-age pigs.. BMC Vet Res 2011 Jul 26;7:41.
- Ho TD, Ellermeier CD. PrsW is required for colonization, resistance to antimicrobial peptides, and expression of extracytoplasmic function u03c3 factors in Clostridium difficile.. Infect Immun 2011 Aug;79(8):3229-38.
- Dubberke ER, Haslam DB, Lanzas C, Bobo LD, Burnham CA, Gru00f6hn YT, Tarr PI. The ecology and pathobiology of Clostridium difficile infections: an interdisciplinary challenge.. Zoonoses Public Health 2011 Feb;58(1):4-20.
- Baker AA, Davis E, Rehberger T, Rosener D. Prevalence and diversity of toxigenic Clostridium perfringens and Clostridium difficile among swine herds in the midwest.. Appl Environ Microbiol 2010 May;76(9):2961-7.
- Giel JL, Sorg JA, Sonenshein AL, Zhu J. Metabolism of bile salts in mice influences spore germination in Clostridium difficile.. PLoS One 2010 Jan 15;5(1):e8740.
- Steele J, Feng H, Parry N, Tzipori S. Piglet models of acute or chronic Clostridium difficile illness.. J Infect Dis 2010 Feb 1;201(3):428-34.
- Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis.. Nat Rev Microbiol 2009 Jul;7(7):526-36.
- Foster DM, Smith GW. Pathophysiology of diarrhea in calves.. Vet Clin North Am Food Anim Pract 2009 Mar;25(1):13-36, xi.
- Besselsen DG, Franklin CL, Livingston RS, Riley LK. Lurking in the shadows: emerging rodent infectious diseases.. ILAR J 2008;49(3):277-90.
- Hammitt MC, Bueschel DM, Keel MK, Glock RD, Cuneo P, DeYoung DW, Reggiardo C, Trinh HT, Songer JG. A possible role for Clostridium difficile in the etiology of calf enteritis.. Vet Microbiol 2008 Mar 18;127(3-4):343-52.
- Rodriguez-Palacios A, Stu00e4mpfli HR, Stalker M, Duffield T, Weese JS. Natural and experimental infection of neonatal calves with Clostridium difficile.. Vet Microbiol 2007 Sep 20;124(1-2):166-72.
Secure Payments
