Efflux pumps directly mediate antibiotic resistance by pumping antibiotic molecules directly out of bacterial cells to keep internal concentrations below toxic levels. Efflux also underpins other mechanisms of antibiotic resistance and affects the rate at resistance mutations are selected. RND efflux pumps are also fundamental to the biology of Gram-negative organisms and are critically important for virulence and biofilm formation. Therefore, inhibitors of efflux pumps would increase susceptibility to antimicrobials, reduce virulence and prevent biofilm formation.
The seminar will discuss work we have done to understand the role of efflux pumps in antibiotic resistance and more broadly how they contribute to the physiology of Gram negative bacteria. This will include progress we have made in finding novel ways to inhibit RND efflux pumps and how we now understand the biological reasons this is so technically challenging. I’ll also discuss recent progress in understanding how efflux works and why the impact on the cell of changes in efflux are so profound.