Imaging of bacterial responses to DNA damage caused by antibacterial agents

In the environment, bacteria are constantlysubjectedto stresses, includingantimicrobial agents such as antibiotics, or toxic effector moleculesdeliveredby a bacterial nanomachinery, the type six secretion system(T6SS). It is known that bacteria under stress exhibit a range of adaptive responses. For example,oxidative stressin the presenceof reactive oxygen species elicitsthe SOS response, a global response to DNA damage.Failure to repair DNAat sites ofoxidative DNA damage,which can be lethal or mutagenic, sometimes leadsto the development of antimicrobialresistance. However, muchremains to be uncovered on the dynamics of the responsesand cell-to-cell heterogeneity, causing variations in cell fates.Inthis project, we will image bacterial responses to DNA damage caused by selectedantibacterial agents, the antibiotic trimethoprim, and T6SS-associated nucleases.In addition, we will investigate the use of protein reportersto understandoxidative stress and DNA damagecaused by diverse antibiotics. This will be done by using cutting-edge microscopy techniques, to visualise key reporter genes at the single cell and single molecule level. The knowledge from this project will allow to decipher and understand further the dynamics involved in the multi-layered toxicity and actions of diverse antibacterial agents.