Switching Off Efflux Pumps to Combat Antibiotic Resistance

Antibiotic Resistance is a global health crisis that kills 700,000 people every year. We now urgently need new antibiotics and novel therapies to treat drug resistant infections. Bacterial efflux pumps are an important mechanism of antibiotic resistance. These are protein machines which sit in the bacterial membrane and pump antibiotic molecules directly out of the cell to keep internal concentrations below toxic levels. The aim of this project is to develop a way to turn off production of these pumps to re-sensitize Gram-negative bacteria to existing antibiotics. In this project we will engineer bacteriophage to deliver a factor to turn off production of this important resistance mechanism. The effect on efflux pump production and antibiotic susceptibility will be measured to assess efficacy of the new technology. Finally, an in vivo animal model system (Zebrafish) will be developed to test the impact in a whole animal model.
This is a collaboration between Dr Jessica Blair (University of Birmingham) and Professor Martha Clokie (University of Leicester). Dr Blair is an expert in mechanisms of antibiotic resistance including bacterial efflux pumps and Prof Clokie is a world expert in bacteriophage biology. During this multidisciplinary project the student will gain expertise from both teams.