Studies of molecular and cellular host-bacteria interactions in relation to bacterial virulence.
Principal investigator; Björck, Lars, Professor, MD/PhD
Clinical speciality: Clinical bacteriology and virology
Co-workers: Matthias Mörgelin, Inga-Maria Frick , Anders Olin, Magnus Rasmussen, Per Åkesson, Oonagh Shannon
Research area/areas: Cell and Molecular Biology, Immunology in the medical area, Infectious Medicine, Medical Biotechnology (focus on Cell Biology (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), Microbiology in the medical area
The relationship between a bacterial pathogen and its human host is based on a multitude of molecular and cellular interactions, which also represent the fundament for bacterial virulence. The aim of our studies is to identify and investigate such interactions to obtain knowledge, that can be utilized in the search for novel therapeutic opportunities in infectious diseases. Bacterial enzymes are also tested as drugs to treat autoimmune conditions.
Over the years we have discovered and characterised several bacterial proteins (proteins G, H, L, Hic, Sic, GRAB, PAB, MtsA, SclA and B) which bind various human proteins (immunglobulins, albumin, fibrinogen, alfa-2-macroglobulin, etc) with high affinity and specificity. These interactions are utilised to study structural prerequisits for protein-protein interactions in general by physico-chemical techniques. The biological and pathogenic significance of interactions between bacterial proteins and components of the immune, coagulation, complement, and contact systems, is also investigated. Bacterial surface proteins assemble and activate the contact system leading to the release of the potent proinflammatory peptide bradykinin. Bacterial proteins also form complexes with human plasma proteins that activate netrophils with profound pathophysiological consequences, and they interfere with complement activation, blood coagulation and other proteolytic events which significantly affect the host-bacteria realtionship. In addition, bacteria produce proteinases that directly affect this relationship. A further analysis of this complex molecular and cellular interplay could shed light on mechanisms contributing to bacterial virulence and thereby identify novel diagnostic and therapeutic opportunities.
The further analysis of these molecular and cellular interactions could identify novel diagnostic and therapeutic targets in infectious diseases. Moreover, bacterial enzymes with a unique specificity for IgG antibodies have been shown to be powerful drugs in animal models of IgG-driven autoimmune diseases.
Link to project homepage: http://www.med.lu.se/klinvetlund
5 recent original publications
Egesten Arne, Frick Inga-Maria, Mörgelin Matthias, Olin Anders, Björck Lars
Binding of albumin promotes bacterial survival at the epithelial surface.
The Journal of biological chemistry. 2011; 286: 2469-2476
Kahn, F., Mörgelin, M., Olin, A.I., Shannon, O.,Herwald, H., Norrby-Teglund, A., and Björck, L.
Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.
PLoS Pathogens. 2008; 4: e1000149
Johansson, B.P., Shannon, O. and Björck, L.
IdeS - a bacterial proteolytic enzyme with therapeutic potential.
PLoS ONE. 2008; 3: e1692
Frick, I.-M., Åkesson, P., Herwald, H:, Mörgelin, M., Malmsten, M., Nägler, D.K., and Björck, L.
The contact system - a novel branch of innate immunity generating antimicrobial peptides.
EMBO J.. 2006; 25: 5569-5578
Herwald, H., Cramer, H., Mörgelin, M., Russell, W., M., Sollenberg, U., Norrby-Teglund, A., Flodgaard, H., Lindbom, L., and Björck, L.
M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage.
Cell. 2004; 116: 367-379
Further publications here (new window)
|Total financing:||9.8 MSEK||Gov grant for clinical research ("ALF"):||3.2 MSEK|
|Total external financing:||4.1 MSEK||Natl and intl prioritized grants:||1.7 MSEK|