We wish to understand, at different molecular levels, the mechanisms that make certain Gram-negative bacteria infectious, and consequently provide the scientific basis for new ways to combat them. The overriding objective is to develop new drug targets, but the work may also yield new tools for biotechnology. The studies concentrate on trimeric autotransporter adhesins.

Adhesins constitute a class of proteins that use the type V (so called autotransporter) secretion system in order to be exposed on the cell surface in Gram-negative bacteria. The family of autotransporter adhesins contains more than 800 members and constitutes the largest family of Gram-negative bacteria extracellular proteins. Depending on the geometry of secretion via the outer membrane (OM) autotransporters were divided into three subgroups: Va – monomeric (classical), Vb – two-partner system, Vc – trimeric. They all nonetheless share same architecture in which the translocation domain (beta-barrel anchored in the OM) and passenger domain (surface exposed) can be distinguished.


In trimeric autotransporter adhesins (TAAs) the passenger domain is highly variable in sequence and size (200 – 3000 amino acid residues), and confers activity and specificity. It is involved in colonisation, interaction with host cell receptors, attachment to epithelial cells, adherence, proteolysis, biofilm formation, serum resistance and cytotoxicity - activities that are important in pathogenicity. In this domain three main regions may be distinguished: stalk, connector and head. Depending on size TAAs may possess many connectors and heads. The translocation domain is much more conserved. It is composed of 12 beta-strands forming a barrel. There is a linker region between translocator and passenger, which is a short helix partly embedded in the barrel that fills the pore.

Currently the most complete structure of a TAA passenger domain is of EibD, solved by us (1). The Eib proteins from Escherichia coli bind in non-immune manner IgG Fc, and IgA, promote serum resistance and are involved in adherence to epithelial cells. The structure, essentially complete from head to membrane anchor, includes both the IgA and the IgG binding sites.

Yersinia enterocolitica adhesin YadA, found in enteropathogenic species of Yersinia, is another TAA for which we solved the crystal structure of the collagen-binding domain (2). Apart from collagen binding YadA also mediates adhesion to other molecules of the extracellular matrix. In addition, YadA is involved in serum resistance, phagocytosis resistance, binding to epithelial cells and autoagglutination. It is an essential virulence factor of Y. enterocolitica, and removing this protein from the bacteria leads to avirulence.

The ribon diagrams of YadA

(A) A general topology model of YadA created based on the experimental structure of the head region and modelled stalk and anchor regions. (B) The crystal structure of the YadA head domain from Y. enterocolitica (1P9H). (C) The top view presents trimeric organisation of YadA.

1. J. C. Leo et al., The structure of E. coli IgG-binding protein D suggests a general model for bending and binding in trimeric autotransporter adhesins. Structure 19, 1021 (2011).
2. Nummelin, H. et al. The Yersinia adhesin YadA collagen-binding domain structure is a novel left-handed parallel beta-roll. EMBO J 23, 701-711 (2004).