Project B03

Mechanisms driving persistence of Yersinia pseudotuberculosis in lymphoid tissues of the intestinal tract

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Prof. Dr. Petra Dersch

 

Enteric yersiniae have evolved strategies to efficiently colonise the intestinal tract and to disseminate into underlying lymphoid tissues. The predominant form of Yersinia pseudotuberculosis infection in humans and other mammalian hosts causes gastrointestinal disorders, such as diarrhea, enteritis and mesenteric lymphadenitis. The infection is usually self-limiting in humans and the pathogens are successfully cleared by the host immune system. However, evidence exists that yersiniae can also persist in the gut-associated lymphoid tissue for several years, causing chronic ileitis, relapsing enteritis and the development of reactive arthritis. Why and how enteropathogenic yersiniae persist in these patients over the long-term is unclear. To establish a persistent infection in the lymphoid tissue, the bacteria have to reprogramme expression of their virulence traits, adapt metabolic pathways to use available nutrients, and activate stress responses and defence strategies to efficiently evade immune surveillance. However, the molecular determinants of the host that trigger these processes at a certain time and at a specific location of the intestinal tract are largely unknown. To gain a better understanding of the establishment of a persistent bacterial infection, we aim to elucidate the molecular decision points that drive Yersinia from the acute phase into persistency during the course of the infection. Based on our preliminary data, we hypothesise that reprogramming of the expression of bacterial factors that reduce inflammation and modulate the function of immune cells during the acute phase allow immune evasion, survival, local spreading and long-term persistence of the pathogen in gut-associated lymphoid tissues. Elucidation of the molecular decision points that define the dynamics and spatial development of persistency will enable us, in close exchange with other projects of the consortium that focus on bacterial persistence, to identify Yersinia-specific but also common drivers of bacterial persistence which can serve as basis for therapeutic approaches.