Bugs on drugs: the use of the Drosophila melanogaster gut microbiome to study bacterial antibiotic tolerance in a complex in vivo condition

Antibiotics have revolutionized medical practice. Soon, however, simple infections will once again kill millions and lead to outrages economic losses. Indeed, antibiotic resistance is on the rise, enabling bacterial growth in the presence of antibiotics. In addition, bacteria also resort to another defense mechanism, tolerance. Bacterial populations, for example, rely on a subset of antibiotic-tolerant persister cells that simply sit out a lethal storm. Antibiotic tolerance is inherent to all bacteria, causes therapy failure, evolves rapidly to extreme levels under antibiotic stress and catalyzes resistance development. Despite its importance, it is neglected by the clinic. Most alarming is how our fundamental view on tolerance mechanisms and their evolution is biased towards artificial, in vitro culture conditions. In this project, I aim to fill this void by exploiting the permissive association between D. melanogaster and gut microbes to study bacterial antibiotic tolerance in a complex in vivo condition. Combining experimental evolution, TnBarSeq and microbial GWAS and in vivo microscopy will result in an understanding of antibiotic tolerance mechanisms relevant in vivo and the identification of its genetic determinants. Simultaneously, the project will result in an easy-to use in vivo model system for future high-throughput studies. Together, in the future, the results of this project might constrain the antibiotic crisis and improve treatment outcome of patients.