Membrane Stress Enhances Specific PQS-Lipid Interactions That Drive Bacterial Outer Membrane Vesicle Biogenesis

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Membrane Biology

Background:

• Gram-negative bacteria utilize outer membrane vesicles (OMVs) for various functions, including toxin delivery and communication.
• The precise mechanisms governing OMV biogenesis are not fully understood, though the Bilayer Couple model offers a framework.
• The Pseudomonas Quinolone Signal (PQS) is implicated in OMV formation, but its specific interactions with membrane lipids are unclear.

Purpose of the Study:

• To investigate the role of specific functional groups of PQS in stimulating OMV biogenesis.
• To elucidate the molecular interactions between PQS and membrane lipids that drive OMV formation.

Main Methods:

• Utilized chemical analogs to probe the function of PQS.
• Employed computational modeling to analyze PQS-lipid interactions.
• Investigated OMV induction in response to PQS modifications.

Main Results:

• All functional groups of PQS are required for OMV induction.
• PQS preferentially interacts with the outer membrane leaflet, particularly with Lipid A.
• Increased hydrogen bonding between PQS and Lipid A explains PQS preference for the outer leaflet.
• PQS accumulation in the crowded outer leaflet drives membrane curvature and OMV formation.

Conclusions:

• The complete structure of PQS is critical for its ability to induce OMV biogenesis.
• PQS-Lipid A interactions in the outer membrane leaflet are key to OMV formation.
• This study provides a molecular basis for PQS-mediated OMV production in Gram-negative bacteria.