Bacteria possess the possibility to become transiently tolerant to a variety of drugs and to other otherwise lethal external agents and conditions. This phenomenon is known as persistence. The persister phenotype is present in a small fraction of the cells in any bacterial population and consists of a dormant state without growth or cell division and with a minimal metabolism. Although there are likely several routes that can lead to forming a persistent cell, the involvement of bacterial toxin-antitoxin (TA) modules seems to be a recurring theme. TA modules are small operons encoding for two ('toxin' and 'antitoxin') or three (with an additional transcriptional regulator) proteins that together control part of the basic cellular metabolism, e.g. the rates of translation, DNA or RNA synthesis, ... Most organisms encode multiple TA modules that work in synchrony and deletion of multiple TA modules is often required to significantly decrease persistence. In this project, I intend to study as a model system the intertwined regulation of two toxin-antitoxin modules from the human pathogen E. coli O157. This work, which will combine structural biology with biochemistry and in vivo experiments, is expected to provide new fundamental insights into how bacteria control entrance into and exit from the persister state, a key question in microbiology and microbial pathogenesis .