Interactoom analyse van Obg-gemedieerde persistentie in Escherichia coli

Persistence refers to a subpopulation of bacteria with the ability to survive antibiotic treatment for an extended period. Persistence is not restricted to laboratory strains but it is intrinsic to every bacterial population studied to date. Consequently, bacterial persistence is recognized as an important cause of antibiotic treatment failure and chronic infections. The conserved GTPase Obg is recognized as a central regulator of persistence. Obg-mediated persistence proceeds through transcriptional activation of hokB mRNA, followed by HokB pore formation, which results in ATP leakage, membrane depolarization and ultimately the transition to the persistent state. While the functionality of HokB is well understood, more upstream of the pathway it is still unclear whether Obg affects hokB mRNA levels directly, or whether addition interactors are at play. Elucidation of the direct persister interactome of Obg could provide the necessary understanding of this transient phenomenon. By means of in vivo photoreactive crosslinking, putative persister interaction partners of Obg were identified. These interactions were further validated by a combination of conventional interactomic methods. Two hypothetical proteins excelled in all set-ups, neither of them linked to persistence before. Based on these two novel interactors, an expanded Obg-mediated persister model was introduced. In conclusion, the results presented in this thesis yield interesting new insights into Obg-mediated persistence. In time, a better understanding of the persister phenotype may lead to the development of anti-persister therapies, supporting the treatment of chronic infections.

Jaar van publicatie:2020

Toegankelijkheid:Closed