Characterising novel DNA damage repair mechanisms in Staphylococcus aureus

Treatment of bacteria with several classes of antibiotics leads to generation of reactive oxygen species that damages DNA. Single and double-strand DNA breaks result in genetic instability and cell death if not repaired, however at present we lack a full understanding of damage repair pathways.

To address this, I developed a novel CrispR-Cas approach to introduce one single or double-strand break at a defined position on the bacterial chromosome. As proof of concept, I used this to identify novel proteins essential for DNA repair in the model organism Bacillus subtilis. I have now adapted this to study DNA repair in the related bacterium Staphylococcus aureus, a critical drug-resistant pathogen. Importantly, my preliminary data showed that homologs of Bacillus proteins are also indispensable for DNA repair in S.aureus.

I will build on these findings to define the repertoire of proteins essential for S.aureus DNA repair and how they interact with one another during repair processes. I will investigate the requirement of repair pathways for virulence and their potential to be targeted by small molecule inhibitors. Collectively this work will define essential pathways for genome maintenance in an important human pathogen that may serve as targets for antibacterial drug development.