Coicis Semen Reduces Staphylococcus aureus Persister Cell Formation by Increasing Membrane Permeability

Unlike resistant cells, persister cells resist antibiotics due to a decreased cellular metabolic rate and can transition back to normal susceptible cells when the antibiotic is removed. These persister cells contribute to the chronic symptoms of infectious diseases and promote the emergence of resistant strains with continuous antibiotic exposure. Therefore, eliminating persister cells represents a promising approach to significantly enhance antibiotic efficacy. Here, we found that Coicis Semen extract reduced Staphylococcus aureus persister cells at a concentration of 0.5 g/L. Linoleic acid and oleic acid, the major components of Coicis Semen extract, exhibited a comparable reduction in persister cells when combined with three antibiotics: ciprofloxacin, oxacillin, and tobramycin. Conversely, these effects were nullified in the presence of the surfactant Tween 80 (1%), suggesting that the hydrophobic characteristics of linoleic acid and oleic acids play a pivotal role in reducing the number of S. aureus persister cells. Considering the concentration-dependent effects of linoleic acid and oleic acid, the persister-reducing activity of Coicis Semen extract was primarily attributed to these fatty acids. Moreover, Coicis Semen extract, linoleic acid, and oleic acid increased the cell membrane permeability of S. aureus . Interestingly, this effect was counteracted by 1% Tween 80, indicating a close association between the reduction of persister cells and the increase in cell membrane permeability. The identified compounds could thus be used to eliminate persister cells, thereby enhancing therapeutic efficacy and shortening treatment duration. When used in conjunction with antibiotics, they may also mitigate chronic symptoms and significantly reduce the emergence of antibiotic-resistant bacteria.