Pump holds key to antibiotic resistance

Scientists at the University of Cambridge believe that they have found the missing link in the fight against antibiotic resistant bacteria.

The team have finally elucidated the structure of a membrane bound protein pump able to rid the bacterial cell of chemicals and toxins.

The protein pumps - known as efflux pumps - are known to reduce the concentration of toxic substances harmful to the bacteria, to low levels that no longer inhibit bacterial function. These toxic substances include naturally occurring defence mechanisms such as bile salts in the human gut, as well as antibiotic drug therapies used to treat infections. Other types of cells are also know to have efflux pumps, but some bacteria, such as E. coli and Pseudomonas have a double membrane so the efflux pump must be able to cross both membranes to remove the unwanted chemicals.

The researchers from Cambridge, Professors Vassilis Koronakis and Colin Hughes, together with Dr Martyn Simmons have finally uncovered the structure and mechanism of this double membrane efflux pump. The substance is picked up via a transporter protein in the inner membrane and delivered to a “trash chute” or exit duct on the outer membrane. There is a third component, the “adaptor” that opens the exit duct to allow for the speedy ejection of the noxious substance.

Professor Hughes suggests that knowing the structure of the efflux pumps will allow a better understanding of how they work, and this in turn can be used to manipulate future antibiotics so that they can avoid being removed from the bacterial cell by the action of the pump. He says “this new research shows how the bits come together. Knowing the key components and their assembly can open up new therapeutic targets – in particular preventing the pumps from assembling in the first place.”

By Georgina Lavender