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 firstname.lastname@example.org 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
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Jennifer Tomlinson, Royal Society-Research Fellows Enhancement Award (Dec 2017), £94,681
Helen Miller, AB AGri Grant (Dec 2017), £73,600
Simon Walker, Royal Society Enhancement Award (Dec 2017), £10,000
Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
Ralf Richter, Royal Society (Dec 2017), £6,000
Christine Foyer, British Council Newton Fund (Dec 2017), £49,840
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
Neil Ranson, Juan Fontana, Mark Harris, Michelle Peckham, Ralf Richter, Peter Stockley, Patricija Van Oosten-Hawle and colleagues in Engineering, FMH and MAPS, Wellcome Trust Equipment Call (Sep 2017), £418,000
Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000
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
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576
Sheena Radford, Wellcome Trust (Mar 2017), £1,836,482
Beatrice Filippi, Royal Society (Mar 2017), £15,000
Tom Bennett, Royal Society (Mar 2017), £15,000
Jamie Johnston, Royal Society (Mar 2017), £15,000
Ryan Seipke, BBSRC (Feb 2017), £52,116
Mary O'Connell, BBSRC (Feb 2017), £46,986
Hannah Dugdale, NERC (Feb 2017), £504,138
Anastasia Zhuravleva, EPSRC (Jan 2017), £100,792