Interactions between polymyxin B and various bacterial membrane mimics: A molecular dynamics study

Area of Science:

• Microbiology
• Biophysics
• Computational Chemistry

Background:

• Polymyxin B (PMB) is a critical last-resort antibiotic for treating infections caused by Gram-negative bacteria.
• The precise molecular mechanisms underlying PMB's membrane interactions remain incompletely understood.

Purpose of the Study:

• To elucidate the molecular-level interactions of Polymyxin B with bacterial membrane mimics.
• To investigate how lipid composition influences PMB's membrane binding and insertion behaviors.

Main Methods:

• Coarse-grained molecular dynamics simulations were employed.
• Bacterial membrane models with diverse lipid compositions were constructed.

Main Results:

• PMB exhibited lipid-specific interactions, preferring rough mutant lipopolysaccharides (Re LPS) in outer membrane models and cardiolipin/POPG in inner membrane models.
• PMB adsorbed to outer membrane surfaces and inserted into inner membranes, altering membrane structure and lipid mobility.
• Outer membrane-bound PMB disrupted Re LPS organization, while inner membrane insertion reduced phospholipid diffusion.

Conclusions:

• PMB's distinct membrane interaction modes are dictated by lipid composition.
• Understanding these mechanisms provides a basis for designing improved polymyxin-based therapies.
• This research offers molecular insights into PMB's action against Gram-negative bacteria.