MRSA uses decoys to evade a last-resort antibiotic
The superbug MRSA uses decoys to evade a last-resort antibiotic, reveals new research.
The findings, from scientists at Imperial College London, suggest potential new ways of tackling the bacteria, such as interfering with the decoys.
Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for thousands of deaths around the world each year. However, because the bacteria are resistant to many different antibiotics, treatment options are limited, and often ineffective.
One of the few antibiotics that can be used against MRSA is a drug of last resort known as daptomycin. However nearly a third of MRSA infections are not cured by this drug, leaving patients with a poor prognosis.
But until now scientists didn’t know how MRSA managed to survive daptomycin treatment.
In the latest findings, published in the journal Nature Microbiology, a team from Imperial discovered that MRSA releases decoy molecules that allow them to escape being killed by the antibiotic.
The decoys are made of the same type of fat that make up the outer layer of MRSA cells. The antibiotic usually latches onto this fat layer, before drilling a hole through the outer shell and killing the bacteria.
However, when MRSA releases these fatty decoy molecules the antibiotic latches onto these instead, and is deactivated.
Dr Andrew Edwards, lead author from the Department of Medicine at Imperial, explained: “These fat molecules act in a similar way to the decoy flares released by fighter planes to avoid a missile. The antibiotic mistakenly targets the decoys, allowing the bacteria to evade destruction. This is the first time this decoy system has been seen in MRSA.”
Using bacterial cells in the laboratory and mouse experiments, the scientists discovered that only some MRSA bacteria can use this decoy system. The team believe this is why around 30% of infections are not cured by the antibiotic daptomycin.
In these resistant infections, the MRSA bacteria turn off a communication system they normally use to ‘talk’ to each other. This communication system allows the bacteria to release toxins that damage human cells. However, this system also seems to interfere with decoy production.
Dr Edwards, who is based at the Medical Research Council’s Centre for Molecular Bacteriology and Infection at Imperial, explained: “These MRSA bacteria ‘go dark’ and stop all communication. It is the switching off of this communication system that allows the decoys to work so effectively.”
He added: “Our focus now is on understanding more about how these decoys are made and how they can be shut off completely to help daptomycin work better in patients.”
Dr Edwards said that a similar decoy mechanism has been seen in E. coli bacteria. “Our findings suggest we may have underappreciated the importance of this decoy system, and that it probably exists in many other bacteria.”
Further experiments revealed the release of decoys can be partially prevented using a second antibiotic, similar to penicillin, called oxacillin. Although MRSA is resistant to oxacillin, using it alongside daptomycin may allow the latter antibiotic to kill the bug more effectively.
Previous research has suggested penicillin-type antibiotics help daptomycin to kill MRSA – although scientists didn’t know why. A clinical trial using the two antibiotics, led by an Australian team, is currently now underway.
Furthermore, tests revealed that a next generation antibiotic, currently in clinical trials, seems to stop production of the fatty decoys.
“This suggests this new antibiotic may also help daptomycin kill MRSA – which could provide another treatment option for patients” added Dr Edwards.
Dr Jonathan Pearce, head of infections and immunity at the Medical Research Council, which supported the work, said: “In the fight against antimicrobial resistance, we are desperately searching for new ways to treat bacterial infections like MRSA as they dangerously start to become resistant to even last resort antibiotics. This study has uncovered a rather cunning tactic that these and possibly other bacteria use to evade current treatment, and armed with this new knowledge, we can begin to develop new and improved treatments to help tackle what is one of the biggest threats to global health.”
Professor Melanie Welham, Chief Executive of the Biotechnology and Biological Sciences Research Council, added: “This demonstrates the value of research that explores the frontiers of chemical biology in bacteria. Finding the biological mechanisms behind why antibiotics do and don’t work is crucial in the fight against anti-microbial resistance.”
The work was supported by the Medical Research Council, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust.
Notes to editors
The paper: Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids by V. Pader at al is published in Nature Microbiology.
An image of MRSA releasing decoys is available from the Imperial College London media office (see external contact below).
About Imperial College London
Imperial College London is one of the world's leading universities. The College's 16,000 students and 8,000 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for society.
Founded in 1907, Imperial builds on a distinguished past – having pioneered penicillin, holography and fibre optics – to shape the future. Imperial researchers work across disciplines to improve health and wellbeing, understand the natural world, engineer novel solutions and lead the data revolution. This blend of academic excellence and its real-world application feeds into Imperial's exceptional learning environment, where students participate in research to push the limits of their degrees.
Imperial collaborates widely to achieve greater impact. It works with the NHS to improve healthcare in west London, is a leading partner in research and education within the European Union, and is the UK's number one research collaborator with China.
Imperial has nine London campuses, including its White City Campus: a research and innovation centre that is in its initial stages of development in west London. At White City, researchers, businesses and higher education partners will co-locate to create value from ideas on a global scale. www.imperial.ac.uk
About the Medical Research Council
The Medical Research Council (MRC) is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-one MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms.
Wellcome exists to improve health for everyone by helping great ideas to thrive. We’re a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by government, BBSRC invested £473 million in world-class bioscience, people and research infrastructure in 2015-16. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
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