Unraveling persister awakening mechanisms

Persister cells are temporarily antibiotic-tolerant cells that are present in every bacterial population. They can survive antibiotic treatment and once the antibiotic pressure in the environment drops below a critical value, they can exit the persister state and establish a new population. Although persisters were discovered in 1944, their clinical importance has only recently become apparent. Indeed, persister cells are associated with the recalcitrance of chronic infections, such as Lyme’s disease and recurrent lung infections in cystic fibrosis patients. In addition, recent work has demonstrated that persister cells constitute a pool from which resistant mutants can emerge. These discoveries have put an urge on the discovery of anti-persister therapies. 
There are two possible scenarios for eradicating persisters in a clinical setting: killing persisters during the persister state, or triggering persister state exit, which resensitizes the cells to conventional antibiotic therapy. The latter requires insight in the molecular mechanisms underlying persister state exit. Unfortunately, our understanding of this phenomenon is far from complete. The aim of this project is to unravel awakening mechanisms, thereby generating novel fundamental insights in persister awakening. In the long term, the data generated in this project can serve as the starting point for the identification of anti-persister compounds