State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo 315211, PR China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, PR China.
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo 315211, PR China.
Microbiol Res. 2023 May;270:127321. doi: 10.1016/j.micres.2023.127321. Epub 2023 Feb 8.
Vibrio splendidus is an opportunistic pathogen, its pathogenicity continues to be a major aquaculture disease infection problem in many parts of the world. Bacteria can form dormant and persister cells, which may be responsible for the difficulty in treating latent infections. Bacterial persister cells are a small subpopulation with high phenotypic heterogeneity that have the ability to persist in response to high concentrations of antibiotics. In our previous work, we have confirmed tetracycline could induce V. splendidus AJ01 persister cells formation. Here, we show that exogenous adenosine and/or guanosine supply restores susceptibility of AJ01 persister cells to tetracycline, leading to effective killing of this persist subpopulation upon wake-up. Mechanistically, exogenous adenosine and/or guanosine promotes the intracellular ATP level, reduces percentage of cells with protein aggresomes, and destroys membrane stability. In addition, when cells were exposed to tetracycline, we found that cells with small nucleocytoplasmic ratio is easy to survive. Overall, our results support that exogenous adenosine or guanosine could be an effective strategy for treating infections with antibiotic-persist bacteria via regulating persisters cells formation.
灿烂弧菌是一种机会致病菌，其致病性持续成为世界许多地区水产养殖疾病感染的主要问题。细菌可以形成休眠和持久细胞，这可能是导致潜伏感染难以治疗的原因。细菌持久细胞是一个具有高度表型异质性的小亚群，具有在高浓度抗生素存在下持续存在的能力。在我们之前的工作中，我们已经证实四环素可以诱导灿烂弧菌 AJ01 持久细胞的形成。在这里，我们表明外源性腺苷和/或鸟苷的供应恢复了 AJ01 持久细胞对四环素的敏感性，导致在唤醒时有效杀死这种持久亚群。从机制上讲，外源性腺苷和/或鸟苷促进细胞内 ATP 水平，降低具有蛋白聚集物的细胞百分比，并破坏膜稳定性。此外，当细胞暴露于四环素时，我们发现核质比小的细胞更容易存活。总的来说，我们的结果支持外源性腺苷或鸟苷可以通过调节持久细胞的形成，成为治疗抗生素耐药细菌感染的有效策略。
