A lipid zipper triggers bacterial invasion

Area of Science:

• Microbiology
• Cell Biology
• Biochemistry

Background:

• Glycosphingolipids are key membrane components involved in cellular signaling.
• Bacterial pathogens utilize membrane nanodomains for host cell invasion.
• The direct role of glycosphingolipids in membrane invagination during bacterial uptake was unclear.

Purpose of the Study:

• To investigate the direct role of glycosphingolipids in the membrane bending process during bacterial invasion.
• To elucidate the mechanism by which Pseudomonas aeruginosa enters host cells.

Main Methods:

• In vitro experiments using giant unilamellar vesicles containing Gb3.
• Theoretical modeling of adhesion energy.
• In cellulo experiments with P. aeruginosa, including genetic knockouts and receptor depletion.

Main Results:

• A
• lipid zipper
• formed by bacterial LecA and host Gb3 directly triggers plasma membrane bending.
• LecA/Gb3 interaction-mediated zippering is sufficient for complete membrane engulfment of bacteria.
• Bacterial uptake was significantly reduced by inhibiting the LecA/Gb3 interaction, independent of actin polymerization.

Conclusions:

• Glycosphingolipids play a direct role in the initial membrane invagination during bacterial invasion.
• The LecA-Gb3 lipid zipper mechanism is sufficient for bacterial engulfment by host cells.
• This study provides a mechanistic understanding of glycosphingolipid-mediated bacterial entry.