Seo Yena, Kim Minjun, Kim Tae-Jong
Department of Forest Products and Biotechnology, Kookmin University, 77 Jeongneungro, Seongbukgu, Seoul 02707, Republic of Korea.
Forest Carbon Graduate School, Kookmin University, 77 Jeongneungro, Seongbukgu, Seoul 02707, Republic of Korea.
Int J Mol Sci. 2025 Jun 30;26(13):6335. doi: 10.3390/ijms26136335.
Persister cells are a subset of bacterial cells that exhibit transient antibiotic tolerance without genetic resistance, contributing to the persistence of chronic infections. This study investigates the ability of diosgenin, a naturally occurring steroidal saponin, to inhibit persister cell formation in through metabolic suppression and membrane modulation. Diosgenin treatments at 80 µM and 160 µM significantly reduced persister cell survival under oxacillin, ciprofloxacin, and gentamicin stress, with reductions ranging from 82% to 94% after 3 h diosgenin pre-exposure. Gene expression analysis revealed that diosgenin downregulated and , key genes involved in (p)ppGpp synthesis, by up to 60%, accompanied by 36-38% decreases in intracellular ATP levels. Diosgenin did not significantly alter membrane permeability or membrane potential but reduced membrane fluidity by 35% and 41% at 80 µM and 160 µM, respectively. Taken together, our findings suggest that diosgenin exerts a dual-action regulatory effect on persister cell formation by disrupting metabolic pathways essential for dormancy and altering membrane dynamics, potentially affecting membrane-associated signaling. This study provides a framework for the further exploration of diosgenin as a potential anti-persister agent with particular promise for use in combination with conventional antibiotics to enhance therapeutic efficacy against chronic bacterial infections.
持留菌是细菌细胞的一个亚群，它们表现出短暂的抗生素耐受性但没有基因抗性，这导致了慢性感染的持续存在。本研究调查了薯蓣皂苷元（一种天然存在的甾体皂苷）通过代谢抑制和膜调节来抑制持留菌形成的能力。在80 μM和160 μM浓度下，薯蓣皂苷元处理显著降低了在苯唑西林、环丙沙星和庆大霉素胁迫下持留菌的存活率，在薯蓣皂苷元预暴露3小时后，存活率降低幅度为82%至94%。基因表达分析表明，薯蓣皂苷元使参与（p）ppGpp合成的关键基因 和 下调高达60%，同时细胞内ATP水平降低36% - 38%。薯蓣皂苷元并未显著改变膜通透性或膜电位，但在80 μM和160 μM浓度下分别使膜流动性降低了35%和41%。综上所述，我们的研究结果表明，薯蓣皂苷元通过破坏休眠所必需的代谢途径并改变膜动力学，对持留菌形成发挥双重调节作用，这可能会影响与膜相关的信号传导。本研究为进一步探索薯蓣皂苷元作为一种潜在的抗持留菌剂提供了框架，其特别有望与传统抗生素联合使用，以提高对慢性细菌感染的治疗效果。
