Detecting antibiotic-induced DNA damage in bacteria by single-molecule DNA microscopy

Research Project, 2022 – 2024

In this porject, we are working on establishing a method to detect different types of DNA damage in bacterial cells using single-molecule DNA microscopy. This method allows detecting individual DNA damage sites on a single DNA molecule. While general bacterial DNA damage reporters exist, most methods are indirect and determining the specific type of DNA damage has so far not been possible. We aim to overcome these limitations and develop a method that can be used on both bacterial cells and on isolated bacterial DNA, allowing distinction between direct and secondary effects. This is a considerable advantage over the current state-of-the-art.

The end goal of theproject is to detect DNA damage induced by antibiotics. DNA-damaging agents are typically discarded from antibiotic development for their expected toxicity, but certain compound classes do target DNA and are selective for bacterial cells. Yet, virtually nothing is known about how such compounds damage DNA. In light of the current antibiotic resistance crisis, it is pivotal not do prematurely discard drug candidates, so a re-evaluation of DNA-targeting compounds as antibacterial agents is in order. Our new method could help greatly with that.