Lipid Specificity of the Fusion of Bacterial Extracellular Vesicles with the Host Membrane
Ashutosh Prince1, Anuj Tiwari1, Titas Mandal2
1Department of Life Sciences, National Institute of Technology, Rourkela 769008, India.
Abstract:
Bacterial membrane vesicles (MVs) facilitate the long-distance delivery of virulence factors crucial for pathogenicity. The entry and trafficking mechanisms of virulence factors inside host cells are recently emerging; however, whether bacterial MVs can fuse and modulate the physicochemical properties of the host lipid membrane and membrane lipid parameter for fusion remains unknown. In this study, we reconstituted the interaction of bacterial MVs with host cell lipid membranes and quantitatively showed that bacterial MV interaction increases the fluidity, dipole potential, and compressibility of a biologically relevant multicomponent host membrane upon fusion. The presence of cylindrical lipids, such as phosphatidylcholine, and a moderate acyl chain length of C16 help the MV interaction. While significant binding of bacterial MVs to the raft-like lipid membranes with phase-separated regions of the membrane was observed, however, MVs prefer binding to the liquid-disordered regions of the membrane. Furthermore, the elevated levels of cholesterol tend to hinder the interaction of bacterial MVs, as evident from the favorable excess Gibbs free energy of mixing bacterial MVs with host lipid membranes. The findings provide new insights that might have implications for the regulation of host machinery by bacterial pathogens through manipulation of the host membrane properties.
Insights
Bacterial membrane vesicles (MVs) fuse with host membranes, altering their properties like fluidity and dipole potential. This interaction influences how pathogens manipulate host cells.
Area of Science:
- Microbiology
- Biophysics
- Cell Biology
Background:
- Bacterial membrane vesicles (MVs) are key for delivering virulence factors.
- Mechanisms of MV entry and trafficking into host cells are under investigation.
- The impact of bacterial MVs on host lipid membrane physicochemical properties remains largely unknown.
Purpose of the Study:
- To investigate the fusion of bacterial MVs with host cell lipid membranes.
- To quantitatively assess the modulation of host membrane properties by bacterial MVs.
- To understand the lipid parameters influencing bacterial MV-host membrane interactions.
Main Methods:
- Reconstitution of bacterial MV and host cell lipid membrane interactions.
- Quantitative analysis of membrane fluidity, dipole potential, and compressibility.
- Investigation of lipid composition effects (e.g., phosphatidylcholine, cholesterol) and acyl chain length.
Main Results:
- Bacterial MV fusion increases host membrane fluidity, dipole potential, and compressibility.
- Cylindrical lipids (e.g., phosphatidylcholine) and C16 acyl chains facilitate MV interaction.
- MVs preferentially bind to liquid-disordered membrane regions over raft-like regions.
- Elevated cholesterol levels hinder bacterial MV interaction with host membranes.
Conclusions:
- Bacterial MVs actively modulate host membrane physicochemical properties upon fusion.
- Specific lipid compositions and structures influence the interaction dynamics.
- Findings suggest a mechanism for bacterial pathogens to manipulate host machinery via membrane alteration.
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