Resistance to antimicrobial drugs is a rapidly looming threat to global health. While drug discovery and inititatives to curb excessive antibiotic use are crucial, it is also important to understand the fundamentals of how drug resistance happens. To do this, we first need to understand how antibiotic drugs work in the first place. Although for most drugs we know what cellular process they target (eg protein production), we know surprisingly little about how drug action interacts with the physiology of the bacterial cell.

 

In my work, together with Philip Greulich, Matt Scott and Martin Evans, we measured how the efficacy of several ribosome targeting antibiotics changed as the bacterial growth environment changed. This is relevant because, in the body, different bacterial infections might well be subjected to different growth environments. We found, surprisingly, that some antibiotics worked well on fast-growing cells while others worked better on slow-growing cells. Using a simple mathematical model, we were able to rationalise this observation. Our model suggests that drugs that are transported into the bacterial cell and bind to ribosomes irreversibly behave quite differently to those that are transported and bind reversibly.

 

We are currently working to apply these ideas to a wider class of problems involving bacteria-antibiotic interactions.