Understanding the early pathogenesis of necrotic enteritis in chickens

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Understanding early pathogenesis and virulence of Clostridium perfringens An increasing consumer pressure is forcing animal agriculture to develop alternatives, or at least to substantially reduce the amount of antibiotics used. We must find effective tools to prevent necrotic enteritis, a deadly disease from affecting antibiotic-free chickens. This disease is caused by pathogenic strains of Clostridium perfringens, but predisposing factors are necessary to create an intestinal environment conducive to an increase in the abundance of C. perfringens (Cp). Another part of the disease process is thought to rely on the ability of NE-causing strains to displace non-pathogenic commensal isolates from the gut of chickens. Numerous Gram positive bacteria have been shown to produce various proteinaceious toxic compounds called bacteriocins, and inhibiting the growth of closely related strains. Perfrin has been identified in pathogenic netB positive NE-causing strains and thought to play an important role. When testing various Cp strains on agar spot test, we observed that not all netB positive Cp strains carry the perfrin gene, that bacteriocins other than perfrin were produced, and that some commensal Cp strains can inhibit the growth of pathogenic Cp strains. We have developed an in vivo ligated intestinal loop model reproducing necrotic enteritis in chickens and noted that lesion severity was correlated with numbers of Cp rods lining the intestinal villi (Parent et al, 2016). Thus, Cp attachment to the enterocyte might play a role in the pathogenesis of NE hence our interest in type IV pilins which are known to play a role in adherence to cell surface. We have recently showed that these pilins are also immunogenic when injected in birds. All of these recent findings, have led to the development of this suggested research program. The proposed work is innovative, using a unique Cp strains bank with access to a new animal model (ligated intestinal loop model) to train highly qualified personal in the rapidly developing field of genomics, transcriptomics and bioinformatics. It will provide unique answers and bring new solutions to an ethical problem, which is the use of antibiotics to grow chickens. This proposal represents a logical continuity of the research program on further understanding necrotic enteritis I have been conducting in the past years. The objectives of my research program are to better understand the pathogenic mechanisms underlying the early infection steps of NE, more precisely 1) identify and characterize two new Cp bacteriocins, 2) verify the protective efficacy of three type IV pilins in a necrotic enteritis model, 3) use our ligated intestinal loop model to identify genes involved in early pathogenesis and their effects on the host, using immunohistochemistry, biological markers and bacterial transcriptomics.