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Survival and pathogenic potential of stress exposed Campylobacter jejuni in eukaryotic cell and murine model

C. jejuni infects humans by colonizing the mucus layer of the intestine followed by adherence and invasion of epithelial cells. In order to survive and adapt to unfavorable conditions, C. jejuni has evolved systems to sense and respond environmental stimuli. Since there are not many publications documenting the links between environmental stress responses and virulence in gram-negative bacteria we investigated food and clinical isolates of C. jejuni after heat shock, starvation and oxidative stress exposure. Survival and virulence properties were studied by culturability, viability as well as the ability of adhesion, invasion and intracellular survival within ‘ in vitro’ cell culture model using Caco-2 intestinal cells and murine macrophages J774. Starvation severely impaired C. jejuni culturability but not viability. In starved C. jejuni, adhesion and invasion ability were mostly reduced but intracellular survival varied. While starved cells survived within Caco-2 cells up to 4 days, they were already killed by macrophages 10 h post infection. Heat shock reduced culturability, viability and virulence properties of C. jejuni. Physiological stress response after short oxidative stress increased internalization and intracellular survival of C. jejuni, although the bacteria could not remain viable for extended period within murine macrophages. With additional ‘ in vivo’ experiments in the murine model we investigated the influence of stress response of campylobacters to their virulence potential. We infected BALB/c mice intravenously with C. jejuni following above mentioned stresses and focused on bacterial spreading and tissue invasion. At different time points after infection the number of C. jejuni CFU in liver and spleen of infected mice was determined. Our findings about ‘ in vitro’ and ‘ in vivo’ modulation of C. jejuni virulence in response to environmental stress factors during food processing may be important for better understanding its contamination and infective cycle and thus contribute to improved safety in food supply.

Campylobacter; stress; virulence; cell lines; mice

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