Bacterial Persistence: What Drives the Phenomenon of Antibiotic Survival Through Dormancy?

细菌持久性：是什么驱动抗生素通过休眠存活的现象？

• 批准号: 2100108
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2100108
• 关键词: Bacterial; Persistence; What; Drives; Phenomenon

What are persister cells?Persister cells are metabolically inactive, non-growing bacterial cells. Persisters were first identified by Bigger in 1944, when research carried out on Staphylococcus aureus revealed a subset of cells were not killed by penicillin. While in the persister state, cells do not divide and can withstand hostile environmental conditions such as nutrient deprivation and antibiotic exposure. Once unfavourable conditions have improved, persister cells are able to resume normal growth and generate new populations of readily dividing cells. Since their discovery, persisters have been observed in multiple species of bacteria and can be referred to as multi-drug tolerant survivors.Persister cells naturally occur at low frequencies within bacterial populations. Persisters are present within each phase of population growth; the majority are observed during the stationary-phase. Previous research has shown 1% of Pseudomonas aeruginosa and Escherichia coli cells are in the persistence state during the stationary-phase (Spoering & Lewis, 2001; Lewis, 2007). The low occurring frequency of persisters makes them difficult to accurately detect.The genetic mechanism behind the formation of the persister state is contested. It has however, been widely accepted that there is no variation in the genetic sequence between a persister cell and a healthy growing bacterium within the same population (Balaban et al., 2004). This distinguishes bacterial antibiotic resistance from persistence, where the former is a result of variation in the genome which codes for a desirable trait. Antibiotic resistance occurs when bacteria exchange genetic sequences which encode adapted resistance, or from advantageous mutations within the bacterial genome. Bacteria such as the gram-negative bacterium Pseudomonas aeruginosa also have intrinsic resistance. This is achieved through having small pores in the cell wall - reducing permeability to antibiotics, and increased efflux pumps - enabling the cell to actively pump out toxins.

什么是持久性细胞？持留细胞是代谢不活跃、不生长的细菌细胞。1944年，比格首次发现了持久性金黄色葡萄球菌，当时对金黄色葡萄球菌进行的研究显示，青霉素不能杀死一部分细胞。在持续状态下，细胞不会分裂，可以承受恶劣的环境条件，如营养缺乏和抗生素暴露。一旦不利的条件得到改善，持留细胞能够恢复正常生长，并产生新的易于分裂的细胞群。自发现以来，已在多种细菌中观察到持留细胞，并可将其称为多药耐受幸存者。持留细胞在细菌群体中以低频率自然出现。持续存在于种群增长的每个阶段;大多数在稳定阶段观察到。先前的研究表明，1%的铜绿假单胞菌和大肠杆菌细胞在稳定期处于持续状态（Spoering &刘易斯，2001;刘易斯，2007）。持续状态的低发生频率使得它们很难被准确地检测出来。持续状态形成背后的遗传机制存在争议。然而，已被广泛接受的是，在同一群体内，在持留细胞和健康生长的细菌之间的遗传序列中不存在变异（Balaban等人，2004年）。这将细菌抗生素耐药性与持久性区分开来，前者是基因组中编码期望性状的变异的结果。当细菌交换编码适应性抗性的遗传序列时，或来自细菌基因组内的有利突变时，抗生素抗性发生。革兰氏阴性菌铜绿假单胞菌等细菌也具有内在耐药性。这是通过细胞壁中的小孔来实现的-减少抗生素的渗透性，并增加外排泵-使细胞能够主动泵出毒素。