This study demonstrates that polymyxin B and polysorbate 80, a non-ionic surfactant, act synergistically against Pseudomonas aeruginosa regarding bacterial leakage, death, and lysis. Polysorbate 80 alone was non-toxic to bacteria. The enhancement of polymyxin activity occurred across all tested polysorbate concentrations (0.0001 to 0.250%), with the greatest rate of enhancement occurring below the critical micelle concentration. The onset of polysorbate's enhancement was rapid, suggesting direct physical rather than metabolic effects on bacteria. Notably, exposure to polysorbate did not increase bacterial uptake of polymyxin. The researchers propose that polysorbate 80 alters the outer lipid structure of P. aeruginosa's envelope, facilitating easier access of polymyxin to the underlying cell membrane where polymyxin exerts its primary antimicrobial effects. This work extends previous observations about polysorbate 80's effects on bacterial permeability and provides mechanistic insight into how surfactants can enhance antibiotic efficacy.

Key findings

• Polymyxin B and polysorbate 80 act synergistically against Pseudomonas aeruginosa in inducing bacterial leakage, death, and lysis across a wide concentration range
• The enhancement of polymyxin activity by polysorbate occurs rapidly and does not correlate with increased polymyxin uptake by bacteria
• Polysorbate 80 likely works by altering the lipid structure of the bacterial envelope, improving polymyxin access to the cell membrane rather than affecting the antibiotic's cellular uptake
• The greatest enhancement effect occurs at or below the critical micelle concentration, suggesting the surfactant's primary effects are not micelle-dependent