The role of the lectin LecB in the interaction of Pseudomonas aeruginosa with epithelia

• Applicant: Professor Dr. Winfried Römer
• Subject Area: Cell Biology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 274827328

The opportunistic pathogen Pseudomonas aeruginosa is a major cause of nosocomial infections. P. aeruginosa infections become increasingly difficult to treat because the bacterium can rapidly adapt to new antibiotics and environmental conditions. In order to enhance infection, P. aeruginosa subverts the polarity of epithelial cells. The bacterium produces the fucose-specific lectin LecB, which has previously been identified as virulence factor. However, the detailed role of LecB during infection is unknown.In preliminary studies we found that purified LecB was sufficient to recapitulate the disruption of epithelial polarity that has been observed during infection with whole P. aeruginosa. In particular, apically applied LecB activated PI3K/Akt-signaling and induced basolateral patches at the apical plasma membrane whereas basolaterally applied LecB caused integrin internalization and complete loss of cell polarity. The aim of this project is to clarify how LecB subverts receptors and signaling networks in order to facilitate P. aeruginosa infection of epithelia. First, we will identify the LecB interactome by mass spectrometry and lipid-based methods. Complementary biochemical and light microscopy-based techniques will allow us to investigate signaling and trafficking events that occur after application of purified LecB, LecB-coated beads, and wt as well as LecB-deficient P. aeruginosa strains. The project will contribute a better understanding of the functions of the virulence factor LecB and will help to devise novel treatment strategies for P. aeruginosa infections.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Roland Thünauer