Persistence is a natural phenomenon whereby a subset of a population of isogenic bacteria either grow slow or become dormant conferring them with the ability to withstand various stresses including antibiotics. In a clinical setting bacterial persistence often leads to the recalcitrance of various infections increasing the treatment time and cost. Additionally, some studies also indicate that persistence can also pave way for the emergence of resistant strains. In a laboratory setting this persistent phenotype is enriched in nutritionally deprived environments. Consequently, in a batch culture the late stationary phase is enriched with persistent bacteria. The mechanism of persister cell formation and its regulation is not well understood. Toxin-antitoxin (TA) systems have been implicated to be responsible for bacterial persistence and rifampicin is used to treat highly persistent bacterial strains. The current study tries to explore a possible interaction between rifampicin and the MazEF TA system that furthers the former’s success rate in treating persistent bacteria. In the current study we found that the population of bacteria in the death phase of a batch culture consists of metabolically inactive live cells resembling persisters, which showed higher membrane depolarization as compared to the log phase bacteria. We also observed an increase in the expression of the MazEF TA modules in this phase. Since rifampicin is used to kill the persisters, we assessed the interaction of rifampicin with MazEF complex. We showed that rifampicin moderately interacts with MazEF complex with 1:1 stoichiometry. Our study suggests that the interaction of rifampicin with MazEF complex might play an important role in inhibition of persisters.

中文翻译：

---

MazEF-利福平相互作用提示利福平诱导的持久性抑制机制

持久性是一种自然现象，同基因细菌群体的一部分会缓慢生长或变得休眠，从而赋予它们抵御各种压力（包括抗生素）的能力。在临床环境中，细菌的持久性常常导致各种感染的顽固性，增加了治疗时间和成本。此外，一些研究还表明，持久性也可以为耐药菌株的出现铺平道路。在实验室环境中，这种持久表型在营养匮乏的环境中富集。因此，在分批培养中，晚期固定相富含持久性细菌。持久性细胞形成的机制及其调控机制尚不十分清楚。毒素-抗毒素（TA）系统被认为与细菌的持久性有关，利福平被用于治疗高度持久的细菌菌株。当前的研究试图探索利福平和MazEF TA系统之间可能存在的相互作用，从而提高前者在治疗持久性细菌方面的成功率。在当前的研究中，我们发现分批培养物死亡阶段的细菌种群由类似持久性物质的代谢惰性活细胞组成，与对数期细菌相比，它们表现出更高的膜去极化作用。我们还观察到该阶段MazEF TA模块的表达增加。由于利福平用于杀死持久性物质，因此我们评估了利福平与MazEF复合物的相互作用。我们显示，利福平与MazEF复合物适度相互作用，比例为1：1化学计量。我们的研究表明，利福平与MazEF复合物的相互作用可能在抑制持久性中起重要作用。