Functional analysis of the head region of Yersinia adhesin YadA in regard to adherence and pathogenicity of Yersinia enterocolitica

• Applicant: Dr. Nikolaus Ackermann
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 179003065

Yersinia enterocolitica and Y. pseudotuberculosis are enteropathogenic bacteria causing diseases ranging from self-limiting diarrhoea to sepsis. In the mouse model yersiniae pass the gut via M cells and invade Peyer´s patches with subsequent septic dissemination. The trimeric autotransporter Yersinia adhesin A (YadA) is an essential mouse virulence (MV) factor for Y. enterocolitica, but not for Y. pseudotuberculosis. It forms a lollipop-like structure with a head (H), connector, stalk and membrane anchor (MA). H is a functionally complex module binding polymorphonuclear cells (PMN) with its N-terminal tip domain (NTTD), and mediating bacterial autoaggregation (AA), extracellular matrix (ECM) and epithelial cell adhesion with its collagen binding domain (CBD). We found that H is dispensable for serum resistance (SR), but essential for MV. Its NTTD influenced in vivo PMN interactions and fibronectin (FN) binding and showed sequence variations between different Yersinia species, serotypes, and strains. To study the effect of H variations of YadA on AA, ECM and cell adherence, interaction with FN and FN fragments, PMN and complement, SR, and MV, we introduced yadA variant genes into Y. enterocolitica strain WA-314. For defining the minimal N-terminal part required for functional YadA we will also construct NTTD deletion mutants and study the interaction of YadA and PMN with recombinant YadA NTTD deletion constructs, as well as phagocytes and serum from CD18, complement component 3 (C3), and plasma FN knockout mouse strains and search for YadA receptors on PMN.

• DFG Programme: Research Grants