Research lead
Scientists at Cambridge University say they have discovered the final element in the structure of efflux pumps that enable bacteria to export antibiotic drugs out of their cells.
The finding provides an insight into one mechanism by which bacteria develop resistance to drugs and could inform the development of new strategies for preventing antibiotic resistance. Efflux pumps evolved as a natural survival mechanism, however bacteria now use the pumps to expel many antibiotics.
Vassilis Koronakis and Colin Hughes at Cambridge have spent two decades studying the structure and function of these pumps and have now elucidated their complete structure, making it possible to build a complete picture of how bacteria expel antibiotics.
Salmonella and other gram-negative bacteria, such as E. coli and Pseudomonas, are bound by two membranes, meaning the efflux pumps must traverse both membranes to pump substances out. The bacterial pumps pick up drugs via a transporter in the inner membrane, which delivers them to an exit duct, TolC, in the outer membrane. A third component, or adaptor, connects these two components, opening the TolC exit duct to eject drugs out of the cell. The researchers have now elucidated this whole tripartite structure.
Hughes suggests the research presents new possibilities for developing antibiotics. “Knowing the key components and their assembly can open up new therapeutic targets - in particular by preventing the pumps assembling in the first place.”
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