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bioRxiv · 10.1101/2022.04.17.488572

The bacterial lectin LecA from P. aeruginosa alters membrane organization by dispersing ordered domains

Sych, T.·Omidvar, R.·Ostmann, R.·Schubert, T.·Brandel, A.·Richert, L.·Mely, Y.·Madl, J.·Roemer, W.
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Abstract

The assembly and dynamic reorganization of plasma membrane nanodomains (also known as "lipid rafts") play key roles in host cell infection by human pathogens (e.g. viruses and bacteria). Viruses and bacteria can trigger the reorganization of lipid rafts which leads to membrane invaginations and downstream signaling that promote infection. Such reorganizations can be induced by interactions of bacterial or viral carbohydrate proteins (so-called lectins) with lipid raft glycosphingolipids (GSLs). Here, we studied the GSL globotriaosylceramide (Gb3) which is a key receptor involved in the cellular uptake of the gram-negative bacterium P. aeruginosa. The bacterial surface lectin LecA targets Gb3 and promotes bacterial invasion via the "lipid zipper" mechanism. However, the impact of LecA on the organization of membrane nanodomains is unknown yet. We mimicked of the plasma membrane using supported lipid bilayers (SLBs) that contained liquid-ordered (Lo, "raft-like", enriched in sphingolipids and GSLs) and liquid-disordered (Ld, "non-raft-like" enriched in DOPC) lipid domains. Upon interaction with LecA, the Lo domains in the SLBs reshaped and dispersed. Moreover, deformation of SLBs was observed as LecA formed membrane multilayers on SLBs surface. We further dissected this process to reveal the impact of Gb3 structure, bilayer composition and LecA valence on the Lo reorganization.

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Sych, T., Omidvar, R., Ostmann, R., Schubert, T., Brandel, A., Richert, L., Mely, Y., Madl, J., Roemer, W.. 2022-04-17. The bacterial lectin LecA from P. aeruginosa alters membrane organization by dispersing ordered domains. https://doi.org/10.1101/2022.04.17.488572

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