Abstract
Various pathogens use receptors on the host's plasma membrane for their cellular uptake. For the bacterium Pseudomonas aeruginosa, interactions between its lectin LecA and the host cell glycosphingolipid globotriaosylceramide (also known as Gb3) are crucial for its internalization via the so-called lipid zipper mechanism. In this study, we investigated the interactions of the P. aeruginosa strain PAO1 with phase-separated lipid bilayers containing Gb3. Surprisingly, bacteria are mostly bound to the interphase of liquid-ordered (Lo) and liquid-disordered (Ld) membrane domains. Simultaneously with the formation of bacterial aggregates and the accumulation of membrane lipids, the lipid bilayers were drastically reorganized and Lo domains were dissolved. Surprisingly, Gb3 was found to play a role in the localization of the bacterium at the interface, less so LecA. When microspheres were used as a minimal mimic of the bacterium, these beads also localized preferentially at the Lo-Ld phase boundaries, but in contrast to living bacteria, beads were unable to cause membrane reorganization and dissolution of the Lo domain, even when coated with LecA. Targeting phase boundaries as "weak points" in membranes and thereby reorganizing and destabilizing the host cell plasma membrane could be an attractive entry strategy for P. aeruginosa and many other bacteria and viruses.