To infect or not to infect: molecular determinants of bacterial outer membrane vesicle internalization by host membranes

Abstract

Outer membrane vesicles (OMVs) are spherical liposomes that are secreted by almost all forms of Gram-negative bacteria. The nanospheres contribute to bacterial pathogenesis by trafficking molecular cargo from bacterial membranes to target cells at the host-pathogen interface. We have simulated the interaction of OMVs with host cell membranes to understand why OMV uptake depends on the length of constituent lipopolysaccharide macromolecules. Using coarse-grained molecular dynamics simulations, we show that lipopolysaccharide lipid length affects OMV shape at the host-pathogen interface: OMVs with long (smooth-type) lipopolysaccharide lipids retain their spherical shape when they interact with host cell membranes, whereas OMVs with shorter (rough-type) lipopolysaccharide lipids distort and spread over the host membrane surface. In addition, we show that OMVs preferentially coordinate domain-favoring ganglioside lipids within host membranes to enhance curvature and affect the local lipid composition. We predict that these differences in shape preservation affect OMV internalization on long timescales: spherical nanoparticles tend to be completely enveloped by host membranes, whereas low sphericity nanoparticles tend to remain on the surface of cells.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC=\"FIGDIR/small/763334v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (44K):\norg.highwire.dtl.DTLVardef@14a3d06org.highwire.dtl.DTLVardef@ec62e9org.highwire.dtl.DTLVardef@151c2f5org.highwire.dtl.DTLVardef@d698d7_HPS_FORMAT_FIGEXP M_FIG C_FIG