Review
Predisposing factors and prevention of Clostridium perfringens-associated enteritis

https://doi.org/10.1016/j.cimid.2013.05.001Get rights and content

Abstract

Clostridium perfringens is one of the major causes of intestinal disease in humans and animals. Its pathogenicity is contributed to by the production of a variety of toxins. In addition, predisposing environmental factors are important for the induction of C. perfringens-associated enteritis as shown by infection models. Environmental contamination, gastric and intestinal pH, intestinal microflora, nutrition, concurrent infections, and medical interventions may influence the intestinal colonization, growth, and toxin production by C. perfringens. Prevention of C. perfringens-associated enteritis may be mediated by the use of feed additives like probiotics, prebiotics, organic acids, essential oils, bacteriophages, lysozymes, bacteriocins, and antimicrobial peptides. Here we summarize and discuss published data on the influence of different environmental predisposing factors and preventive measures. Further research should focus on feed composition and feed additives in order to prevent C. 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.

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