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

To infect or not to infect: molecular determinants of bacterial outer membrane vesicle internalization by host membranes
To infect or not to infect: molecular determinants of bacterial outer membrane vesicle internalization by host membranes
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.
0022-2836
1251-1264
Jefferies, Damien
8df97e21-8df6-4571-bfbe-3edc41e16967
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Jefferies, Damien
8df97e21-8df6-4571-bfbe-3edc41e16967
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

Jefferies, Damien and Khalid, Syma (2020) To infect or not to infect: molecular determinants of bacterial outer membrane vesicle internalization by host membranes. Journal of Molecular Biology, 432 (4), 1251-1264. (doi:10.1016/j.jmb.2020.01.008).

Record type: Article

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.

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Accepted/In Press date: 6 January 2020
e-pub ahead of print date: 11 January 2020
Published date: 14 February 2020

Identifiers

Local EPrints ID: 441906
URI: http://eprints.soton.ac.uk/id/eprint/441906
ISSN: 0022-2836
PURE UUID: 61c2fc52-9fe3-41e5-b2ef-52a24f12e788
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

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Date deposited: 02 Jul 2020 16:30
Last modified: 11 Jan 2021 05:01

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