MRSA's double defence against antibiotics

• Researchers at the University of Sheffield have discovered the superbug Methicillin Resistant Staphylococcus aureus (MRSA) requires two mechanisms to be able to survive exposure to high levels of antibiotics
• In addition to the established route that uses a new enzyme to make its cell walls, MRSA has also evolved an alternative division mechanism that allows it to replicate in the presence of antibiotics
• MRSA is an AMR superbug that is a serious medical problem, causing over 120,000 deaths per annum
• The next step in the research will be working towards developing inhibitors that can target MRSA’s novel survival strategy

Scientists have discovered the mechanism which allows the superbug Methicillin Resistant Staphylococcus aureus (MRSA) to become highly resistant to antibiotics, paving the way for new approaches to control infectious disease.

MRSA is an antimicrobial resistance (AMR) superbug that causes over 120,000 deaths per year. Given the urgent need for new, more effective antibiotics and a lack of MRSA vaccines, understanding and combating the superbug is crucial.

The new research, led by the University of Sheffield, reveals MRSA has a double defence mechanism against antibiotics - this new insight offers hope in treating the life-threatening superbug and other infectious diseases.  

Bacteria, such as MRSA, have mesh like cell walls around them that require enzymes to knit them together.  The enzymes are the targets for antibiotics such as penicillin and methicillin.  This type of antibiotic has saved millions of lives over the decades. 

It has been known for many years that in order to be resistant, MRSA has acquired a new cell wall enzyme that allows it to survive exposure to antibiotics. However, the Sheffield researchers have found that this alone is insufficient for survival. 

The new study shows MRSA has also evolved an alternative division mechanism that allows it to replicate in the presence of antibiotics. This previously unknown mechanism is essential for MRSA resistance. By understanding the details of this process, researchers are working towards developing inhibitors that can target MRSA’s novel survival strategy.

Professor Simon Foster from the University of Sheffield’s School of Biosciences said: “This research is very exciting as it has not only uncovered a new mechanism for MRSA, that was hiding in plain sight, but also the ability of the bacteria to divide in an alternative way.

“These findings have important ramifications for the development of new antibiotics, but also for understanding the fundamental principles that underpin bacterial growth and division.  

“This will provide new ways to tackle this dangerous infectious organism.”

Professor Jamie Hobbs from the University of Sheffield’s School of Mathematical and Physical Sciences said: “This is a fantastic example of how physics and biology can be brought together to understand the pressing societal challenge of antimicrobial resistance.  We could not have made the discoveries without this synergy, fusing world leading microscopy, with genetics and microbiology.

“Our research demonstrates the power of an interdisciplinary approach to address the basic mechanisms supporting the physics of life which are of such importance to healthcare”.

The next step for this research is to determine how MRSA is able to grow and divide in the presence of antibiotics using the new mechanism that has been discovered. This research involves a multidisciplinary collaboration, led by the University of Sheffield with international partners and funded by Wellcome and UKRI.