The ability of non-resis­tant bacte­r­ial pathogens to survive antibi­otics during infec­tion (toler­ance) contributes not only to global rise of antibi­otic resis­tance, but also to chron­i­cal relapse of infec­tions. The aim of the project is to under­stand what contributes to bacte­r­ial revival after antibi­otic treat­ment and the under­ly­ing biolog­i­cal pathways. The findings of this project will contribute to better informed decisions on the selec­tion of antibi­otics to treat infec­tions and prevent relapse.

Antibi­otic resis­tance is a global health­care crisis with severe socio-economic conse­quences. In suscep­ti­ble bacte­r­ial species, antibi­otics fail to elimi­nate a small subpop­u­la­tion (known as toler­ant bacte­ria) which are able to toler­ate clini­cal doses of antibi­otics. This is differ­ent from resis­tance which is typified by ability of the bacte­ria to grow in the presence of antibi­otics. Toler­ant bacte­ria revive after antibi­otic treat­ment and are able to resume growth and cause chronic relapse of infec­tions. Toler­ance is known to be initi­ated by metabolic stress among others, however, little is known about the mecha­nisms that trigger revival of toler­ant subpopulations.

This project aims to unravel the molec­u­lar mecha­nism that elicit bacte­r­ial revival after antibi­otic treat­ment. To this end, I will develop high-through­put approaches to system­at­i­cally inves­ti­gate revival of the pathogen Salmo­nella Typhimurium, a model organ­ism for infec­tion biology. To further test the in vivo relevance of my project, I will re-assess whether bacte­r­ial revival is triggered differ­ently inside murine macrophages, which are the preferred host niche during systemic salmonellosis.