Proteins of the ABC-F protein family are a major source of antibiotic resistance in ‘superbugs’ such as Staphylococcus aureus, a group of bacteria that includes MRSA.
Ordinarily, the ribosome is an ideal target for antibiotics because living bacteria cannot grow without it, but when bacteria produce ABC-F proteins many antibiotics no longer work.
Until now, there has been a longstanding debate as to exactly how these proteins work.
Scientists have been divided in their support for two separate ideas; that the proteins are pumps that remove antibiotics from bacterial cells, or that they interact with the bacteria’s ribosomes to stop antibiotics from blocking them.
Fundamental research of this type provides a better picture of the molecular basis for antibiotic resistance. It can offer valuable information that might be used in the future to design antibiotics to bypass antibiotic resistance, when scientists are able to understand more about the properties that allow drugs to enter bacterial cells.
Dr Liam Sharkey, a Fellow in the School of Molecular and Cellular Biology, who carried out the research, said: “These findings provide the first direct evidence that these proteins directly protect the ribosome. As a result the goal-posts of our research have changed, we can now zoom-in and try to work out the exact details of how this protection is happening.
“Our results suggest that the proteins work by removing antibiotics when they bind their targeted ribosome. It’s a bit like the proteins are bouncers at a ribosome nightclub, the bouncer’s job is to keep kicking out antibiotics that are trying to get in and cause trouble.”
This debate has been not settled until now because of the technical challenges associated with the research and much of the attention of academics in the field has been focused on the idea that these proteins are working as pumps.
The University of Leeds has played a key role in the birth of structural biology as a scientific discipline, with the development of X-ray crystallography by Nobel Laureates William and Lawrence Bragg in Leeds in 1912-13.
A new academic symposium, the Astbury Conversation, is being hosted at the University of Leeds from 11 – 12 April 2016, to bring together leading researchers from across the globe to discuss the most recent innovations, new techniques and technologies in the field of structural molecular biology.
A public exhibition and lecture on Tuesday 12 April follows the symposium, aimed at helping people understand the secret life of molecules.
Professor Michael Levitt, who was awarded the 2013 Nobel Prize in Chemistry for developing computer-based tools to better understand and predict chemical reactions, will be delivering the talk, “How modelling molecules builds our understanding of life.”
Dr Liam Sharkey is available for interview. Contact the University of Leeds press office on email@example.com or call 0113 343 4031.
A copy of the paper is available on request.
For further information about the University’s investment in structural biology, read more here
Helen Miller, Innovate UK (Apr 2018), £999,960
Elisabetta Groppelli, David Rowlands & Stanley Lemon (University of North Carolina), Medical Research Foundation Fellowship (Apr 2018), £293,494
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Julie Aspden, Royal Society (Apr 2018), £20,000
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Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
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Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
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