Acylation of the RTX toxin MbxA stimulates host membrane disruption through a specific interaction with cholesterol

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Repeat-in-Toxin (RTX) toxins are pore-forming proteins secreted by gram-negative bacteria.
• These toxins disrupt host cell membranes, contributing to bacterial pathogenesis.
• Acylation of lysine residues is known to enhance RTX toxin hemolytic activity, but the mechanism is poorly understood.

Purpose of the Study:

• To investigate the role of acylation in the pore-forming mechanism of the RTX toxin MbxA.
• To elucidate how acylation influences MbxA interactions with cell membranes and cholesterol.

Main Methods:

• Comparative analysis of acylated and non-acylated MbxA.
• In vitro membrane disruption assays.
• Experiments using living cells to observe MbxA-induced membrane damage.

Main Results:

• Acylation of MbxA enhances its lytic activity and pore formation.
• Acylation promotes specific interactions between MbxA and cholesterol.
• Acylation is not required for initial membrane binding but significantly boosts pore formation.

Conclusions:

• Acylation is a critical factor enhancing RTX toxin-mediated membrane disruption.
• The interplay between lipid composition (sterols), acylation, and toxin activity is crucial for MbxA pathogenesis.
• These findings provide molecular insights into RTX toxin mechanisms and host-pathogen interactions.