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

Abstract

The dynamic reorganization of plasma membrane nanodomains (lipid rafts) plays a key role in host cell infection by human pathogens. Bacteria can induce the reorganization of lipid rafts as a result of the interactions between bacterial lectins and lipid raft glycosphingolipids (GSLs). However, it is still unclear how such interactions trigger the initial stage of the infection mechanism. Here, we study the GSL globotriaosylceramide (Gb3), 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 a lipid zipper mechanism. We mimic the plasma membrane using supported lipid bilayers (SLBs), containing liquid-ordered and liquid-disordered lipid domains. We observe that the liquid-ordered domains in the SLBs disperse upon interaction with LecA, accompanied by a deformation of SLBs surface. Our results link the membrane reorganization triggered by LecA with the P. aeruginosa infections in host cells.

The mechanistic basis of the membrane‐permeabilizing activities of the virulence‐associated protein A (VapA) from Rhodococcus equi

“…A possible mechanism for the formation of V h domains is the VapA-induced establishment of lipid patches on the membrane cross-linked by VapA. This phenomenon has been described for the interaction of LecA with Gb3containing DOPC:SM:Chol bilayers (Sych et al, 2023).…”