Comparative Immunology, Microbiology and Infectious Diseases
ReviewPredisposing factors and prevention of Clostridium perfringens-associated enteritis
Introduction
Clostridium perfringens, a gram-positive spore-forming anaerobic bacterium, has been implicated as one of the major pathogens in the development of humans and animal intestinal diseases and has been frequently diagnosed as the cause of human-foodborne disease [1], [2]. The bacterium lacks the ability to produce 13 of the 20 essential amino acids and obtains sufficient amounts of these amino acids by degrading host tissue via its toxins and degradative enzymes [3]. C. perfringens is classified into five toxinotypes (A–E), based on the production of four major toxins: alpha-, beta-, epsilon-, and iota-toxin [1]. Besides these four major toxins, the bacterium may produce additional toxins, such as enterotoxin, beta2 toxin, and NetB toxin [1], [4], [5]. Of the five toxin types, C. perfringens type A is the most common toxin type and is widespread in the environment and in the intestine of both healthy and diseased animals and humans [1], [6]. C. perfringens type A is part of the normal intestinal flora in the gastrointestinal tract which comprises a complex mixture of microbes including at least hundreds of bacterial species [7], [8], [9]. C. perfringens types other than type A are less frequently cultured from the intestinal tract of animals and humans and can only occasionally be isolated from the environment in areas where clostridial disease is present [1]. The heat resistant spores of C. perfringens can survive in the environment for years [10].
The pathogenesis of C. perfringens-associated enteritis is complex and still under investigation [11]. The significance of some of the toxins produced by C. perfringens in the development of enteritis has been determined by deletion studies, e.g. the significance of NetB in the development of necrotic enteritis in broilers and the significance of enterotoxin in the development of food-borne enteritis in humans [5], [12]. The role of some other toxins like iota toxin or beta2 toxin in the development of intestinal disease is still under debate. C. perfringens, beside the production of toxins, may suppress certain members of the normal intestinal flora which confer a health benefit to the host. Such a disbalance of the intestinal microflora may accelerate disease progression [13], [14]. Furthermore, environmental circumstances may directly or indirectly influence the normal intestinal flora, the colonization, growth, and toxin production of virulent C. perfringens strains, and subsequently the occurrence of intestinal disease [1], [15].
Different environmental predisposing factors may play a role in different animal species and humans and the significance of risk factors may variate among C. perfringens toxin types and subsequent diseases. However, many predisposing factors have been shown to play a role among diverse C. perfringens toxin types and in several animal species and humans. Therefore a comparative approach may increase the awareness of possible predisposing factors which is important in lowering the prevalence of outbreaks [16]. In this review, possible predisposing factors which influence intestinal colonization, growth, toxin production of C. perfringens, and the development of C. perfringens-associated intestinal disease, and preventive measures are summarized and discussed.
Section snippets
Extracellular influence on survival, growth, and toxin production
The transcription of a variety of genes of C. perfringens that encode for proteins required for intracellular metabolism, cell survival and multiplication, i.e. enzymes, transporters, and toxins, is regulated by the two-component VirR/VirS system [38]. The proteins VirS and VirR act as a transmembrane protein and a response regulator protein regulating expression of the genes encoding alpha toxin, beta toxin, beta2 toxin, NetB toxin, and subsequently the production of these toxins [39], [40],
Environmental contamination
Although C. perfringens is a normal inhabitant of the intestine, virulent strains from the environment may displace resident C. perfringens strains in the gut [17], [18] or transfer plasmids that contain a toxin encoding gene to C. perfringens strains residing in the intestinal tract, converting these resident strains into potential enteropathogens [19], [20]. Preventing oral uptake of virulent strains is thus considered to be a useful prophylactic [17]. Faeces of infected animals and humans
Probiotics
Bacterial species that may confer a health benefit to the host after oral administration e.g. by inhibition of harmful bacteria are called probiotics [171]. The inhibition of harmful bacteria is mediated by competition for nutrients, lowering of the pH, and the production of specific antibacterial substances [172], [173], [174], [175], [176]. The in vitro activity against C. perfringens by potentially probiotic bacterial species is listed in Table 1. Probiotic strains should be harmless to the
Summarizing conclusion
C. perfringens is ubiquitous in the environment and in the intestinal tract of animals and humans and is frequently involved in the development of enteritis. Faeces of infected animals and contaminated meat are the most common sources of infection. Environmental factors are thought to influence the colonization, intestinal growth, and toxin production by C. perfringens and might play a key-role in the development of disease.
Colonization, growth, and toxin production are increased by high levels
Acknowledgements
Arie van Nes and Linda McPhee are acknowledged for critical reading of the manuscript.
References (287)
Clostridia as agents of zoonotic disease
Veterinary Microbiology
(2010)- et al.
Beta2 toxin, a novel toxin produced by Clostridium perfringens
Gene
(1997) - et al.
Clostridium perfringens: toxinotype and genotype
Trends in Microbiology
(1999) - et al.
Identification of changes in the composition of ileal bacterial microbiota of broiler chickens infected with Clostridium perfringens
Veterinary Microbiology
(2010) - et al.
Changes in the caecal microflora of chickens following Clostridium perfringens challenge to induce necrotic enteritis
Veterinary Microbiology
(2012) - et al.
Necrotic enteritis-producing strains of Clostridium perfringens displace non-necrotic enteritis strains from the gut of chicks
Veterinary Microbiology
(2008) - et al.
Intra-species growth-inhibition by Clostridium perfringens is a possible virulence trait in necrotic enteritis in broilers
Veterinary Microbiology
(2009) - et al.
Clostridium perfringens and foodborne infections
International Journal of Food Microbiology
(2002) - et al.
Genetic diversity of Clostridium perfringens isolated from healthy broiler chickens at a commercial farm
Veterinary Microbiology
(2008) - et al.
Foaling-management practices associated with the occurrence of enterocolitis attributed to Clostridium perfringens infection in the equine neonate
Preventive Veterinary Medicine
(2000)
Risk profiles of pork and poultry meat and risk ratings of various pathogen/product combinations
International Journal of Food Microbiology
Clostridium perfringens in retail chicken
Anaerobe
Identification of a two-component VirR/VirS regulon in Clostridium perfringens
Anaerobe
The VirR/VirS regulatory cascade affects transcription of plasmid-encoded putative virulence genes in Clostridium perfringens strain 13
FEMS Microbiology Letters
Influence of porcine intestinal pH and gastric digestion on antigenicity of F4 fimbriae for oral immunisation
Veterinary Microbiology
Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea
Best Practice & Research. Clinical Gastroenterology
Effects of dietary protein source and level on intestinal populations of Clostridium perfringens in broiler chickens
Poultry Science
Dietary protein source and manufacturing processes affect macronutrient digestibility, fecal consistency, and presence of fecal Clostridium perfringens in adult dogs
The Journal of Nutrition
Dietary glycine concentration affects intestinal Clostridium perfringens and lactobacilli populations in broiler chickens
Poultry Science
Dietary encapsulated glycine influences Clostridium perfringens and lactobacilli growth in the gastrointestinal tract of broiler chickens
The Journal of Nutrition
Effect of different dietary methionine sources on intestinal microbial populations in broiler chickens
Poultry Science
Evaluation of different fluids for detection of Clostridium perfringens type D epsilon toxin in sheep with experimental enterotoxemia
Anaerobe
Effects of diet and antimicrobials on growth, feed efficiency, intestinal Clostridium perfringens, and ileal weight of broiler chicks
Poultry Science
Influence of a wheat diet on mortality of broiler chickens associated with necrotic enteritis
Poultry Science
The effect of added complex carbohydrates or added dietary fiber on necrotic enteritis lesions in broiler chickens
Poultry Science
Colonization of the intestinal tract by Clostridium perfringens and fecal shedding in diet-stressed and unstressed broiler chickens
Poultry Science
Effects of diet type and enzyme addition on growth performance and gut health of broiler chickens during subclinical Clostridium perfringens challenge
Poultry Science
Barley inclusion and avoparcin supplementation in broiler diets. 2. Clinical, pathological, and bacteriological findings in a mild form of necrotic enteritis
Poultry Science
Clostridial enteric diseases of domestic animals
Clinical Microbiology Reviews
Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater
Proceedings of the National Academy of Sciences of the United States of America
NetB, a new toxin that is associated with avian necrotic enteritis caused by Clostridium perfringens
PLoS Pathogens
Gut microorganisms, mammalian metabolism and personalized health care
Nature Reviews. Microbiology
Role of human microflora in health and disease
European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the Eurpoean Society of Clinical Microbiology
Quantitative analysis of the intestinal bacterial community in one- to three-week-old commercially reared broiler chickens fed conventional or antibiotic-free vegetable-based diets
Journal of Applied Microbiology
Freshwater suspended sediments and sewage are reservoirs for enterotoxin-positive Clostridium perfringens
Applied and Environmental Microbiology
Necrotic enteritis in broilers: an updated review on the pathogenesis
Avian Pathology
Inactivation of the gene (cpe) encoding Clostridium perfringens enterotoxin eliminates the ability of two cpe-positive C. perfringens type A human gastrointestinal disease isolates to affect rabbit ileal loops
Molecular Microbiology
Significance of beta 2-toxigenic Clostridium perfringens infections in animals and their predisposing factors – a review
Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health
Clostridium perfringens in poultry: an emerging threat for animal and public health
Avian Pathology
Spread of a large plasmid carrying the cpe gene and the tcp locus amongst Clostridium perfringens isolates from nosocomial outbreaks and sporadic cases of gastroenteritis in a geriatric hospital
Epidemiology and Infection
Epidemiology of diarrhoea caused by enterotoxigenic Clostridium perfringens
Journal of Medical Microbiology
Bacterial contamination of computer keyboards in a teaching hospital
Infection Control and Hospital Epidemiology: the Official Journal of the Society of Hospital Epidemiologists of America
Incidence of Clostridium perfringens in broiler chickens and their environment during production and processing
Avian Diseases
High mortality in egg layers as a result of necrotic enteritis
Avian Diseases
Clostridial enteric infections in pigs
Journal of Veterinary Diagnostic Investigation: Official Publication of the American Association of the Veterinary Laboratory Diagnosticians, Inc
Population-based study of fecal shedding of Clostridium perfringens in broodmares and foals
Journal of the American Veterinary Medical Association
Incidence and tracking of Clostridium perfringens through an integrated broiler chicken operation
Avian Diseases
Clostridium perfringens toxin types from wild-caught Atlantic cod (Gadus morhua L.), determined by PCR and ELISA
Canadian Journal of Microbiology
Large outbreaks of Clostridium perfringens food poisoning associated with the consumption of boiled salmon
The Journal of Hygiene
Clostridium perfringens and its toxins in minced meat from Kars, Turkey
Food Additives and Contaminants
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2020, Aquaculture ReportsCitation Excerpt :For example, in the necrotizing enterocolitis (NEC) of premature infants, the relative abundances of Clostridium sensu stricto, Escherichia, and Shigella were significantly higher (Zhou et al., 2015). In the necrotic enteritis of livestock and poultry, Clostridium perfringens was generally identified at significantly higher levels (Allaart et al., 2013; Shojadoost et al., 2012). In zebrafish, intestinal inflammatory responses were associated with an increase in Cetobacterium and Lactobacillus (Zheng et al., 2019).