Patch repair protects cells from the small pore-forming toxin aerolysin

Area of Science:

• Cellular biology
• Toxicology
• Membrane biophysics

Background:

• Aerolysin toxins damage cell membranes, but the specific repair mechanisms cells employ remain unclear.
• Proposed repair pathways include endocytosis, annexins, MEK-dependent shedding, and patch repair, but their roles against aerolysin are debated.
• The necessity and triggering of calcium (Ca2+) influx during aerolysin-induced membrane damage are controversial.

Purpose of the Study:

• To investigate Ca2+ influx and identify membrane repair mechanisms activated by aerolysin.
• To compare aerolysin's effects with those of cholesterol-dependent cytolysins (CDCs) regarding membrane repair.

Main Methods:

• Assessed cell survival upon removal of extracellular Ca2+.
• Measured Ca2+ influx and intracellular Ca2+ chelation effects.
• Evaluated the roles of caveolar endocytosis, MEK-dependent repair, annexin A6 recruitment, and dysferlin in aerolysin resistance.

Main Results:

• Extracellular Ca2+ removal protected cells from aerolysin, unlike CDCs.
• Aerolysin induced sustained Ca2+ influx, and its chelation increased cell death, indicating Ca2+-dependent repair activation.
• Caveolar endocytosis and MEK-dependent repair did not protect against aerolysin.
• Dysferlin expression conferred protection against aerolysin, suggesting patch repair is involved.

Conclusions:

• Aerolysin triggers a Ca2+-dependent cell death pathway that may mask repair mechanisms.
• Patch repair, involving proteins like dysferlin, is proposed as the primary mechanism resisting aerolysin.
• Different bacterial toxin classes activate distinct cellular membrane repair strategies.