Sphingosine kills bacteria by binding to cardiolipin.

Area of Science:

• Microbiology
• Biochemistry
• Cell Biology

Background:

• Sphingosine, a sphingoid base, exhibits bactericidal activity against pathogens.
• Sphingosine is present in airway epithelial cells, contributing to respiratory defense.
• Previous work established sphingosine's role in airway immunity.

Purpose of the Study:

• To elucidate the rapid bactericidal mechanism of sphingosine.
• To identify the molecular interactions responsible for sphingosine's antimicrobial effects.
• To investigate the role of specific sphingosine chemical groups in bacterial killing.

Main Methods:

• Lipid-binding assays
• Cell biology assays
• Genetic experiments involving cardiolipin synthase knockout strains
• In vitro and in vivo antimicrobial testing

Main Results:

• Sphingosine rapidly permeabilizes bacterial plasma membranes within minutes.
• This permeabilization leads to ATP and metabolic activity loss, causing rapid bacterial death.
• The protonated amino group (NH2) of sphingosine is essential for its bactericidal activity.
• Sphingosine's NH2 group binds to negatively charged cardiolipin in bacterial membranes.
• Bacteria lacking cardiolipin synthase are resistant to sphingosine.

Conclusions:

• Sphingosine kills bacteria by targeting cardiolipin in the bacterial plasma membrane.
• Binding of sphingosine to cardiolipin induces membrane clustering, leading to permeabilization and cell death.
• This mechanism highlights sphingosine as a key component of innate immunity against bacterial pathogens.