Miltefosine impacts small molecule transport in Gram-positive bacteria

Area of Science:

• Membrane Biophysics
• Antimicrobial Drug Action
• Bacterial Physiology

Background:

• Miltefosine (MLT), an alkylphosphocholine, is recognized for its anticancer and antiparasitic properties.
• MLT's interaction with eukaryotic lipid rafts is established, with emerging evidence suggesting effects on bacterial membrane microdomains.
• Conflicting reports exist regarding MLT's influence on bacterial plasma membrane fluidity.

Purpose of the Study:

• To investigate the impact of MLT on the global ordering and lipid packing of Staphylococcus aureus membranes.
• To determine how MLT affects the transport of various small molecules across the membranes of Staphylococcus aureus and Bacillus subtilis.

Main Methods:

• Steady-state fluorescence techniques, including generalized polarization of laurdan and anisotropy of diphenylhexatriene, were used to assess membrane properties.
• Time-resolved second harmonic scattering was employed to study the transport of small molecules across bacterial membranes.

Main Results:

• Miltefosine (MLT) was found to have no significant effect on the overall ordering and lipid packing of Staphylococcus aureus membranes.
• MLT significantly altered the transport of certain small molecules across the membranes of S. aureus and B. subtilis, though not all molecules were affected.

Conclusions:

• MLT does not disrupt the global membrane structure of S. aureus.
• MLT's ability to modulate small molecule transport suggests its potential as an adjuvant for enhancing drug delivery in bacteria.