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  • Final Report Summary - LEC&LIP2INVADE (The interactions of the Pseudomonas aeruginosa lectins LecA and LecB with glycosphingolipids result in membrane invagination, signaling and cellular uptake of the bacterium)
ERC

lec&lip2invade Report Summary

Project ID: 282105
Funded under: FP7-IDEAS-ERC
Country: Germany

Final Report Summary - LEC&LIP2INVADE (The interactions of the Pseudomonas aeruginosa lectins LecA and LecB with glycosphingolipids result in membrane invagination, signaling and cellular uptake of the bacterium)

The bacterium Pseudomonas aeruginosa has emerged as a major opportunistic pathogen during the past century. The invasion of host cells plays a fundamental role in the pathogenesis of this bacterium. As clinically important antibiotic resistance of P. aeruginosa continues to increase, the identification of microbial as well as host cell factors, which are essential for bacterial uptake, is of high significance and may lead to novel therapeutic approaches against bacterial infection.

In the framework of our highly ambitious and interdisciplinary research project at the interface of biology, chemistry and physics, we have discovered a novel entry mechanism of the bacterium P. aeruginosa into non-phagocytic epithelial cells. The tetravalent, galactose-binding P. aeruginosa lectin LecA binds and clusters the host cell glycosphingolipid Gb3. This dynamic ligand-receptor interaction is fully sufficient to induce the engulfment of the bacterium. The invasiveness of the bacterium is reduced by about 70 % if one of these two crucial factors lacks. Based on these findings, we have developed a novel type of divalent glycocompound as inhibitor of LecA, which blocked bacterial invasion almost completely in low nanomolar concentration. Moreover, we have demonstrated that the tetravalent, fucose-binding P. aeruginosa lectin LecB is a master manipulator of host cell processes. It induces diverse host cell signalling pathways (e.g. PI3K/Akt signalling, NFkB signalling) and affects various processes, such as cell migration, autophagy, cell death and inflammation.

Our ERC-funded project has nicely contributed the better understanding of the impact of bacterial lectins on host cell physiology and opens up a new avenue to fight the pathogenesis of P. aeruginosa infections.

Contact

Winfried Römer, (Scientist)
Tel.: +4976120397240
Fax: +4976120397223
E-mail
Record Number: 197996 / Last updated on: 2017-05-12