Scientists may have discovered important step in the fight against antibiotic-resistant bacteria

Imagine falling seriously ill with an infection. Normally, we visit the doctor, are prescribed antibiotics, and after 7-10 days, we're back on our feet. But today, it is no longer guaranteed that the treatment will work. Infections like pneumonia, tuberculosis, or blood poisoning are becoming increasingly difficult to treat, and according to the World Health Organization (WHO), millions of lives could be lost if we don’t find a solution to the so-called MRSA bacteria, that can’t be treated with antibiotics.

When bacteria manage to resist antibiotic treatment, it is often because the bacteria form a biofilm of proteins and sugars that acts as a shield against the antibiotic. And it is a part of the biofilm defence structure that researchers have now decoded in a new study, explains Maria Andreasen, Associate Professor at the Department of Biomedicine at Aarhus University, who is one of the researchers behind the study:

“We have decoded the molecular structure of an important part of a bacterium called S. aureus. This is the first detailed insight into how these specific molecules form their macrostructure. By understanding the structures and how the biofilm forms, we can develop new strategies and treatment methods and perhaps even prevent the bacteria from forming the biofilm altogether.”

A matter of life or death

Although the focus is on molecular cell structures, the researchers are addressing a much larger and far-reaching problem. According to a 2022 study, 1.27 million people globally died in 2019 directly due to infections from antibiotic-resistant bacteria.

This is why the findings from the Aarhus University and University of Pittsburgh study are significant, says Maria Andreasen. 

“For the first time, we have identified the structure of the entire protein from the MRSA biofilm. Now, we can focus our research on how we might use this knowledge to find or develop molecules that prevent the biofilm from forming. If we succeed, it will be easier to treat infections and combat the growing antibiotic resistance,” she says.

If the research team, which also includes researchers from the University of Pittsburgh in the USA, can break down or prevent the formation of the protective biofilm, it will be a crucial step towards treating resistant MRSA infections.

FACTS

What is an MRSA bacterium?

MRSA stands for Methicillin-resistant Staphylococcus aureus. It is a type of bacteria that has developed resistance to many common antibiotics, including methicillin, penicillin, and similar drugs. Here are some key points about MRSA:

• Staphylococcus aureus: A common bacterium that many people carry on their skin or in their noses without becoming ill. However, if it enters the body through a wound, it can cause infections such as boils, wound infections, and, in severe cases, pneumonia or sepsis.
• Resistance: MRSA is dangerous because it is resistant to most common antibiotics. This means that infections caused by MRSA are harder to treat and require stronger or more specialised antibiotics.
• Hospitals and healthcare: MRSA is particularly problematic in hospitals and nursing homes, where people with weakened immune systems, open wounds, or invasive devices (such as catheters) are more vulnerable to infection. It can spread quickly in such environments where people are in close proximity.
• Health consequences: MRSA infections can be very serious and, in some cases, life-threatening, especially if the infection is not treated early or spreads to the bloodstream or vital organs.

What have the researchers decoded?

Researchers from the Department of Biomedicine at Aarhus University, together with researchers at the University of Pittsburgh, have decoded the molecular composition of an important part of the S. aureus biofilm, specifically the aggregated form of PSMα1, which is a functional amyloid. This contributes to forming a protective biofilm that makes the bacterium resistant to antibiotic treatment.

What could this mean for the future treatment of bacterial infections?

A lot more research is needed. However, understanding the precise structure of the molecular composition means that researchers are one step closer to either preventing the biofilm from forming or developing treatments that can penetrate it.

About the study

• Study type: The project is fundamental research conducted mainly using cryo-electron microscopy, supplemented with fluorescence spectroscopy and NMR (nuclear magnetic resonance).  

• Collaborating partners: University of Pittsburgh (Umit Akbey, James F. Conway) and from iNano at Aarhus University (Thomas Boesen and Taner Drace).  

• External funding: The project received external funding from the University of Pittsburgh School of Medicine, Aarhus University Research Foundation, and the Danish National Cryo-EM Facility. 

• Disclosure of potential conflicts of interest:  None.  

• Read more in the scientific article:  https://www.pnas.org/doi/abs/10.1073/pnas.2406775121 <

Contact:

Associate Professor Maria Andreasen  
Aarhus University, Faculty of Health, Department of Biomedicine  
Email: mariaj@biomed.au.dk  
Phone: +45 24 21 14 21