Abstract
To investigate how Campylobacter jejuni causes the clinical symptoms of diarrhoeal disease in humans, use of a relevant animal model is essential. Such a model should mimic the human disease closely in terms of host physiology, incubation period before onset of disease, clinical signs and a comparable outcome of disease. In this study, we used a gnotobiotic piglet model to study determinants of pathogenicity of C. jejuni. In this model, C. jejuni successfully established infection and piglets developed an increased temperature with watery diarrhoea, which was caused by a leaky epithelium and reduced bile re-absorption in the intestines. Further, we assessed the C. jejuni genes required for infection of the porcine gastrointestinal tract utilising a transposon (Tn) mutant library screen. A total of 123 genes of which Tn mutants showed attenuated piglet infection were identified. Our screen highlighted a crucial role for motility and chemotaxis, as well as central metabolism. In addition, Tn mutants of 14 genes displayed enhanced piglet infection. This study gives a unique insight into the mechanisms of C. jejuni disease in terms of host physiology and contributing bacterial factors.
Highlights
C. jejuni and C. coli are able to colonise specific pathogen free pigs, they are limited in their ability to cause clinical signs of disease[9]
In this study we have re-established and characterised in detail a gnotobiotic piglet model to investigate diarrhoeal disease caused by C. jejuni and combined transposon (Tn) mutagenesis with Tn insertion site sequencing (Tn-seq) to identify genes implicated in infection of the piglet gastrointestinal tract
One day post-delivery, piglets were orally challenged with ~5 × 109 colony forming units (CFU) of C. jejuni strains 11168, a human enteritis isolate[17, 81–176], a human campylobacteriosis outbreak isolate[18], or strain L115 that was isolated from a paediatric diarrhoeal disease case[19]
Summary
C. jejuni and C. coli are able to colonise specific pathogen free pigs, they are limited in their ability to cause clinical signs of disease[9]. In a study by Boosinger and Powe, C. jejuni was detected on the surface of epithelial cells as well as sub-mucosal[12] These studies demonstrated that gnotobiotic piglets represent a suitable model to investigate disease mechanisms of C. jejuni as their gastrointestinal anatomy and physiology is similar to humans as well as their susceptibility to many enteric pathogens[6,7,8,10,12,13,14]. The availability of various genome-wide screening methods employing next-generation sequencing technologies enabled detailed assessment of the molecular mechanisms involved in colonisation of chickens and the invasion of epithelial cells[15,16] No such studies have been performed in models mimicking human campylobacteriosis. In this study we have re-established and characterised in detail a gnotobiotic piglet model to investigate diarrhoeal disease caused by C. jejuni and combined transposon (Tn) mutagenesis with Tn-seq (transposon insertion site sequencing) to identify genes implicated in infection of the piglet gastrointestinal tract
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