Persister cells, which are tolerant to antimicrobials, contribute to biofilm recalcitrance to therapeutic agents. In turn, the ability to kill persister cells is believed to significantly improve efforts in eradicating biofilm-related, chronic infections. While much research has focused on elucidating the mechanism(s) by which persister cells form, little is known about the mechanism or factors that enable persister cells to revert to an active and susceptible state. Here, we demonstrate that cis-2-decenoic acid (cis-DA), a fatty acid signaling molecule, is able to change the status of Pseudomonas aeruginosa and Escherichia coli persister cells from a dormant to a metabolically active state without an increase in cell number. This cell awakening is supported by an increase of the persister cells' respiratory activity together with changes in protein abundance and increases of the transcript expression levels of several metabolic markers, including acpP, 16S rRNA, atpH, and ppx. Given that most antimicrobials target actively growing cells, we also explored the effect of cis-DA on enhancing antibiotic efficacy in killing persister cells due to their inability to keep a persister cell state. Compared to antimicrobial treatment alone, combinational treatments of persister cell subpopulations with antimicrobials and cis-DA resulted in a significantly greater decrease in cell viability. In addition, the presence of cis-DA led to a decrease in the number of persister cells isolated. We thus demonstrate the ability of a fatty acid signaling molecule to revert bacterial cells from a tolerant phenotype to a metabolically active, antimicrobial-sensitive state.

中文翻译：

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脂肪酸信号分子 cis-2-decenoic acid 增加代谢活性，并将持久细胞恢复到抗菌敏感状态。

耐受抗微生物剂的持久细胞有助于生物膜对治疗剂的抵抗。反过来，杀死持久细胞的能力被认为可以显着改善根除与生物膜相关的慢性感染的努力。虽然许多研究都集中在阐明持久细胞形成的机制，但对使持久细胞恢复到活跃和易感状态的机制或因素知之甚少。在这里，我们证明了 cis-2-decenoic acid (cis-DA)，一种脂肪酸信号分子，能够将铜绿假单胞菌和大肠杆菌持久性细胞的状态从休眠状态改变为代谢活跃状态，而不会增加细胞数量。数字。这种细胞觉醒得到了持久细胞的增加的支持。呼吸活动以及蛋白质丰度的变化和几种代谢标志物的转录表达水平的增加，包括 acpP、16S rRNA、atpH 和 ppx。鉴于大多数抗菌剂针对活跃生长的细胞，我们还探讨了 cis-DA 对增强抗生素功效的作用，因为它们无法保持持久细胞状态，从而杀死持久细胞。与单独的抗微生物治疗相比，持久性细胞亚群与抗微生物剂和顺式 DA 的组合治疗导致细胞活力显着降低。此外，顺式 DA 的存在导致分离的持久细胞数量减少。因此，我们证明了脂肪酸信号分子能够将细菌细胞从耐受表型恢复为代谢活跃的表型，