Host Acute Stress Responses and the Regulation of C. Jejuni Virulence in the Avian Gut

Campylobacter jejuni is regarded as being a commensal in the chicken gut but work at the University of Bristol challenges this assumption. We have shown that broiler flocks with pre- existing enteric infections and birds subject to stress by either transport and/or thinning are significantly more likely to become infected with Campylobacter and to excrete higher numbers of the pathogen. What is not understood is why stress or infection should have such a marked impact on the susceptibility of chickens to Campylobacter and on the behaviour of the bacterium. <P>
The effects of stress on animals are multi-factorial but what is common to all is that their neurotransmitter levels will be raised. We have shown that one neurotransmitter, noradrenaline (NA), markedly stimulates the growth of C. jejuni, particularly in low iron environments. In fact, the stimulatory effects seen with C. jejuni can exceed those seen with either Salmonella or E. coli, which may reflect the very different behaviour of C. jejuni compared to other enteric pathogens. Campylobacter may be better able to grow in the intestine of an animal under stress because of raised intestinal NA levels. Greater pathogen numbers would result in increased bacterial translocation across the gut epithelium, although other factors may also be important. In low iron conditions, NA increases the number of cells of C. jejuni that are flagellated and this may affect virulence. NA also increases invasion of epithelial cells in vitro. This could be particularly important because approximately 5 percent of chickens on retail sale contain C. jejuni in deep muscle tissues, which could enhance survival during cooking. Gut permeability is also changed by stress in the animal, which may increase translocation of bacteria from the gut. In animals compromised by either stress and/or infection, C. jejuni may behave more like an avian pathogen in that cells become more tissue-invasive. <P>
The proposed work will identify the molecular basis for the effects of NA on C. jejuni, particularly on iron metabolism, interaction with gut tissues and the expression of genes important in the infection of humans and animals. We will identify the bacterial determinants that allow NA to change Campylobacter behaviour. The work will explore the hypothesis that invasion from the gut is more likely when NA is present because the bacteria are better equipped to cross the intestinal epithelium and survive in the submucosa. <P>
A better understanding of the interaction between Campylobacter and the stressed host could eventually enhance animal welfare and improve food safety. Improved understanding of the reasons for the NA-mediated switch from 'commensal' to 'pathogen' may also provide insights into virulence mechanisms in humans. The contaminated farm environment is the main source of Campylobacter entry into poultry flocks. The better bacteria survive in the environment the more likely they are to be transmitted between animal hosts. With this in mind, studies will also be carried out to determine whether Campylobacter cells, pre-exposed to NA, show increased environmental fitness because changes in iron metabolism increase the potential to resist oxidative stress, a major factor in environmental survival.