Global regulators of antibiotic resistance in E. coli and Salmonella: understanding cross-talk and downstream resistance mechanisms (360G-Wellcome-204000_Z_18_A)

Antimicrobial resistance is increasing with alarming speed. As a consequence, even simple surgeries may become impossible due to the risk of infection. As such, this represents a major health crisis. Antibiotic resistance arises because bacteria rapidly adapt to antibiotics in their environment. Adaptation can involve modifying gene expression patterns or acquisition of useful mutations. However, we do not have a complete picture of these pathways to resistance. In this project, we will study four transcriptional regulators that control the so called "multiple antibiotic resistance" response in E. coli and Salmonella. This response allows cells to combat antibiotics and is implicated in clinical levels of resistance. We will identify the key regulatory targets that provide resistance to antibiotics. In doing so, we will shed light on the underlying mechanisms of resistance. We will also determine how widely conserved these resistance mechanisms are and build a complete picture of regulation by understanding cross-talk between the regulators. Ultimately, by identifying new pathways to antibiotic resistance, this work will underpin the development of new treatments for bacterial infections.