Researchers from the School have worked with collaborators in Cambridge to uncover the inner workings of a cellular pump which helps bacterial cells neutralise the effects of antibiotics. This work has implications in the fight against antimicrobial resistance (AMR) and is published today in Nature Microbiology.
Standard antibiotics enter bacteria through channels present in the bacterial cell wall. To protect themselves, bacteria use pumps, known as efflux pumps, also present in the cell wall to pump out any foreign agents such as antibiotics. This is an important feature in bacteria and often results in multi-drug resistance. Channels and pumps can become altered to become more resistant to antibiotic entry and better at efflux, contributing to the growth in AMR. Understanding how these channels and pumps function, could help researchers tackle antimicrobial resistance.
With Professor Ben Luisi’s team in Cambridge, Dr Ulrich Zachariae, Centre for Antimicrobial Resistance and his postdoctoral researcher Dr. Salomé Llabrés have uncovered from E. coli the structure of the whole assembly of one of these efflux pumps. Utilising the new technology of cryo-electron microscopy (cryo-EM), has allowed the complete structure to be seen and is the first known example of an ATP driven pump to be reported. This specialised pump is known to pump out the commonly used antibiotic, erythromycin.
Specifically, in Dundee, they provided understanding of the function of a gating ring found within the channel. This ring acted as a one-way valve. It appears to be closed to the outside, therefore preventing entry of drug molecules into the bacterial cell but drugs already within the cell could slip outwards.
This new knowledge is being taken forward by Dr Zachariae in collaboration with Professor Luisi and Dr Samantha Pitt at the University of St Andrews with funding from Tenovus Scotland. The new study will investigate if modifications or drug binding to this efflux gate are capable of either keeping it shut to prevent the drugs exiting the cell or to open it more widely for inward transport to allow drugs to enter.
The work by Dr Zachariae was supported with funding from SUPA (Scottish Universities' Physics Alliance) and the Wellcome Trust ISSF.
The Centre for Antimicrobial Resistance
The Centre brings together researchers from across the University of Dundee to focus on innovation in tackling antimicrobial resistance.