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

Damien Jefferies1, Syma Khalid1

  • 1School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK.

Insights

Outer membrane vesicles (OMVs) from Gram-negative bacteria interact with host cells. Lipopolysaccharide length dictates OMV shape, influencing whether they are internalized or remain on the cell surface.

Area of Science:

  • Microbiology
  • Biophysics
  • Cell Biology

Background:

  • Outer membrane vesicles (OMVs) are secreted by Gram-negative bacteria.
  • OMVs play a role in bacterial pathogenesis by delivering cargo to host cells.
  • Understanding OMV-host interactions is crucial for deciphering infection mechanisms.

Purpose of the Study:

  • To investigate the impact of lipopolysaccharide (LPS) length on OMV-host cell membrane interactions.
  • To elucidate the mechanisms governing OMV uptake by host cells.
  • To explore how OMV shape influences internalization dynamics.

Main Methods:

  • Coarse-grained molecular dynamics simulations were employed.
  • Simulations focused on the interaction between OMVs and model host cell membranes.
  • Analysis of OMV shape, lipid coordination, and membrane curvature was performed.

Main Results:

  • LPS length significantly affects OMV shape upon interaction with host membranes.
  • Long LPS (smooth-type) OMVs maintain spherical shape, while short LPS (rough-type) OMVs spread.
  • OMVs actively coordinate host ganglioside lipids, altering membrane curvature and composition.

Conclusions:

  • OMV lipopolysaccharide structure is a key determinant of its interaction with host cell membranes.
  • The shape of OMVs influences their internalization pathway and efficiency.
  • These findings provide insights into the biophysical mechanisms of bacterial pathogenesis and OMV-mediated host cell manipulation.

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