Interaction of antibiotics with bacterial cells

Research Project, 2019 – 2023

Antibiotic resistance is a major issue and a serious threat to global health. A large problem in fighting resistance is that our understanding of how antibiotics kill bacteria is still very limited. This is a serious limitation, since this knowledge is pivotal for targeted drug development. So far, antibiotic mechanisms have mainly been studied in vitro with a strong focus on single targets. However, there is increasing evidence that antibiotics inhibit bacteria on multiple levels. For example, established antibiotics like daptomycin and tetracycline have different mechanisms than previously thought and unprecedented additional targets.

It is paramount to understand how the molecular target interaction of an antibiotic leads to either cell death or bacterial adaptation. This central research question is addressed with a focus on the bacterial cell envelope, which is not only a promising antibiotic target structure but also the location of important stress response systems that help bacteria to survive antibiotic exposure. We investigate the influence of antibiotic on the bacterial cell membrane and peptidoglycan cell wall using advanced fluorescence and electron microscopy, spectroscopy, and mass spectrometry. The results from this project will advance our comprehension of the mechanisms behind antibiotic action, which is key to develop sustainable antibacterial strategies.