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Studying pore formation in lipid bilayers induced by the P. aeruginosa lectin LecA

The bacterium P. aeruginosa emerged as a major human opportunistic pathogen during the past decades, maybe as a consequence of its resistance to antibiotics and disinfectants. It is able to cause severe infections of the respiratory and urinary tract, skin and eye, predominantly in immune compromised patients. In addition, P. aeruginosa has a unique ability to cause chronic infections in the lungs of patients with cystic fibrosis, ultimately leading to pulmonary failure and death [1].

P. aeruginosa has a vast range of virulence factors, amongst them, the two bacterial lectins LecA and LecB, which, by virtue of their sugar binding, contribute to the pathogens’ host specificity and adherence to host cells. Recently, we have demonstrated that the interactions of LecA with the host cell glycosphingolipid Gb3 are sufficient to induce the engulfment of the bacterium. Furthermore, the absence of one of these two factors leads to a reduction of invasiveness of the bacterium by around 70%, clearly showing the LecA is more than a simple adhesin [1-3]. 

Figure 1: The crystal structure of the tetrameric P. aeruginosa lectin LecA and the chemical structure of the host cell glycolipid Gb3 are depicted. The interactions of both lead to the invagination of the bacterium in cells and giant liposomes (right image).

Our preliminary experiments on pore-spanning lipid bilayers showed that soluble LecA is able to form transient pores by binding to the glycosphingolipid Gb3. 

Figure 2: Ion conductance recordings performed on a multi-electrode cavity array (16-channel chip). LecA (2.5 µM) somehow forms transient pores (conductivities from less than 200 up to 1500 pA) by binding to Gb3-containing lipid bilayers at a holding potential of 100 mV. The bilayers were composed of 75 mol% DOPC, 20 mol% cholesterol and 5 mol% Gb3.   

The aim of the proposed project is to investigate the mechanism of the formation of transient pores across a lipid bilayer induced by the highly specific binding of soluble LecA to the glycosphingolipid Gb3. This pore induction might be evolutionary beneficial for the bacterium, since it may (1) destabilize the host cell homoeostasis, (2) enable the uptake of bacterial effectors aside from the canonical secretion systems, and (3) facilitate the dissemination of the bacterium depending on the pore size.



[1]   Aigal S, Claudinon J, Römer W (2015) BBA - Molecular Cell Research 1853(4):858-871.
[2]   Eierhoff T*, Bastian B, Thuenauer R, Madl J, Audfray A, Aigal S, Juillot S, Rydell GE, Müller S, de Bentzmann S, Imberty A, Fleck C*, Römer W* (2014) Proc Natl Acad Sci 111(35):12895-12900.
[3]   Novoa A, Eierhoff T, Topin J, Varrot A, Barluenga S, Imberty A*, Römer W*, Winssinger N* (2014) Angew Chem Int Ed 53(34): 8885-8889.



Zheng, S, Eierhoff,  T, Aigal,  S, Brandel,  A, Thuenauer,  R, de Bentzmann,  S, Imberty, A, Römer, W (2017) The Pseudomonas aeruginosa lectin LecA triggers host cell signalling by glycosphingolipid-dependent phosphorylation of the adaptor protein CrkII. Biochimica et Biophysica Acta - Molecular Cell Research. 1864(7): 1236-45.



Prof. Dr. Winfried Römer

Institute of Biology II and Centre for Biological Signalling Studies (BIOSS)
Biologie II, Signalhaus
Schänzlestr. 18
79104 Freiburg

Phone: +49 (761) 203 67500 
Fax: +49 (761) 203 67535