DNA repair and genetic stability: elucidating the effects of cell physiology in Escherichia coli

In all domains of life, cells rely on the correct replication and repair of their chromosomes to transmit genetic information. In bacteria, the importance of these processes is highlighted by the many clinically relevant antibiotics that cause DNA damage resulting in cell death but also in mutations leading to antibiotic resistance. Bacteria can proliferate at very different speeds depending on their environment; some infections are very rapid while others will take much more time to develop. The speed at which bacteria grow affects all the molecular processes necessary for life, yet the connection between bacterial growth and sensitivity to DNA-damaging agents has so far been overlooked. It has been observed that slow growing bacteria are less sensitive to DNA-damaging antibiotics, but the reasons underlying this observation are not known.

By combining experimental and theoretical methods, I aim to elucidate the molecular mechanisms that explain this important phenomenon and to quantify how it affects the acquisition of drug resistance.

My ultimate goal is to discover new ways of manipulating bacterial growth for novel applications in antibiotic therapies.