Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada.
Genes (Basel). 2023 Sep 28;14(10):1887. doi: 10.3390/genes14101887.
Persisters are a small fraction of growth-arrested phenotypic variants that can survive lethal concentrations of antibiotics but are able to resume growth once antibiotics are stopped. Their formation can be a stochastic process or one triggered by environmental cues. In the human pathogen , the canonical peptide-based quorum-sensing system is an inducible DNA repair system that is pivotal for bacterial survival. Previous work has shown that the CSP-signaling peptide is a stress-signaling alarmone that promotes the formation of stress-induced persisters. In this study, we exposed to the CSP pheromone to mimic DNA damage conditions and isolated the antibiotic persisters by treating the cultures with ofloxacin. A transcriptome analysis was then performed to evaluate the differential gene expression between the normal stationary-phase cells and the persisters. RNA sequencing revealed that triggered persistence was associated with the upregulation of genes related to several stress defense mechanisms, notably, multidrug efflux pumps, the arginine deaminase pathway, and the Opu/Opc system. In addition, we showed that inactivation of the VicK kinase of the YycFG essential two-component regulatory system abolished the formation of triggered persisters via the CSP pheromone. These data contribute to the understanding of the triggered persistence phenotype and may suggest new therapeutic strategies for treating persistent streptococcal infections.
持留菌是生长停滞的表型变异体中的一小部分，它们能够在致死浓度的抗生素中存活，但一旦抗生素停止，它们就能够恢复生长。它们的形成可以是一个随机过程，也可以是由环境线索触发的。在人类病原体中，经典的基于肽的群体感应系统是一种诱导型 DNA 修复系统，对细菌的生存至关重要。以前的工作表明，CSP 信号肽是一种应激信号警报素，它促进应激诱导持留菌的形成。在这项研究中，我们用 CSP 信息素来模拟 DNA 损伤条件，并通过用氧氟沙星处理培养物来分离抗生素持留菌。然后进行转录组分析，以评估正常静止期细胞和持留菌之间的差异基因表达。RNA 测序表明，触发持留与与几种应激防御机制相关的基因上调有关，特别是多药外排泵、精氨酸脱氨酶途径和 Opu/Opc 系统。此外，我们还表明，通过 CSP 信息素，YycFG 必需的双组分调节系统的 VicK 激酶失活会消除触发持留菌的形成。这些数据有助于理解触发持留菌表型，并可能为治疗持续性链球菌感染提供新的治疗策略。
