Projects

Carbohydrates play key roles in biological processes. The initial contact between cells is mediated by oligosaccharides and host pathogen interactions often crucially depend on sugar signals being read by lectin receptors, i.e., carbohydrate binding proteins. There are many examples of human pathogens that interact with the host in this way (e.g., Nathan Sharon, BBA 2006). The rise of resistance against antibiotics in bacteria is a major threat and demands the development of novel antibacterial therapies. Blocking the adhesion of pathogens to the host cell is a validated approach to treat infections. Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of death in cystic fibrosis patients. These bacteria form biofilms in the respiratory tract, which leads to increased resistance towards antibiotics. Two bacterial lectins, LecA and LecB that bind α-galactosides and α-fucosides, respectively, were shown to be involved in biofilm formation. Blocking these proteins was shown to be a promising approach towards therapeutics against infections of this pathogen. Our research is focused on structure based rational design and the synthesis of carbohydrate conjugates and mimics thereof, that selectively block LecA and LecB mediated Pseudomonas biofilm formation. The inhibitory capacities of these molecules are assessed in a target-based in vitro assay, as well as in biofilm or agglutination assays.

In a second project, the mechanism of a newly discovered glycosyltransferase family will be analyzed through synthesis of small molecular probes and their evaluation in an established biochemical in vitro assay. Preliminary results showed that a member of this family, a C. elegans glycosyltransferase transferase adds galactose in a beta-1,4-linkage to core fucoses in N-glycans with high specificity (Titz et al., J. Bio. Chem. 2009). Interestingly, also protein sequences of pathogenic origin were found among the members of this family.

• Titz, Alexander - Project leader

• Zukunftskolleg