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

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.