Obg is a highly conserved GTPase that has previously been linked to various cellular processes including ribosome biogenesis, DNA replication and chromosome segregation. Especially intriguing is the recently uncovered role of Obg in bacterial persistence. Persister cells are a subpopulation of bacteria that entered a dormant non-replicative state, hence allowing them to tolerate and survive various stresses including antibiotic treatments. As such these persister cells are believed to be an important cause of many chronic bacterial infections. In addition to Obg’s role in persistence it was recently shown that a mutant allele (obg*) confers cytotoxicity when expressed in Escherichia coli and this via a so-far unknown mechanism. This seems to place Obg on the cross-roads between bacterial survival and cell death pathways, although the underlying cellular networks remain elusive. The current PhD project aims at unravelling the detailed molecular mechanism and pathways linking Obg to both persistence and cell death. Hereto, the structure and function of Obg and Obg* will be investigated and their interactions with previously described and newly discovered interactors will be characterized in detail. Together these results will contribute to an atomic-resolution view of the Obg interactome, which in turn could form the basis for devising
new strategies to fight bacterial infections.