Physics of Life reveals how tiny liquid droplets create 'superbugs'

Posted on Thursday 31 July 2025

Scientists discover how bacteria protect their essential components during stress allowing them to survive antibiotics and the immune response

The study, led jointly by a team in Peking University and Prof Mark Leake at the University of York, reveals how bacteria – many of which result in difficult to treat diseases and infections – use tiny remarkable liquid droplets to evade being killed by antibiotics and the body’s immune response.

The team of scientists used physics and biology to light up these ‘aggresomes’ using intense laser beams to track single protein and RNA molecules inside living bacteria including species such as Escherichia coli which are common to our guts and in urinary tract infections, and Salmonella which are a prevalent cause of food poisoning.

Antimicrobial resistance, or AMR, is a key global health challenges responsible for over 1 million deaths each year, which happens because many germs can turn into very harmful ‘superbugs’ through becoming resistant to antibiotics designed to kill them. This is also particularly harmful if such superbugs develop strategies to also evade the body’s own nature defences of the immune response. But how bacteria actually do this has remained a mystery.

The research has revealed how membraneless droplets form inside bacteria naturally from proteins which pool together as a remarkable liquid in the same way that droplets of oilive form which you shake up a bottle of salad dressing. They act to wrap wrap a type of molecule called RNA which is formed in a crucial step when any gene is read out and actively expel other types of molecules called enzymes which would normally destroy the RNA. The formation of these droplets called ‘aggresomes’ is triggered from imposing stress on the cell such as when bacteria are attacked by white blood cells in our bodies, or by antibiotics.

Co-lead author of the two studies, Professor Mark Leake, from the Physics of Life group at the University of York, said: “Our findings open the lid on how bacteria swaddle crucial RNA when being attacked – this allows them to survive antibiotics and even the ravages our own immune system, and in doing so make it far more likely that these surviving germs will then go onto to become ‘superbugs’.

“We used some amazing technology to shine laser beams onto these aggresomes to allow us to peer inside living bacteria and actually see how these aggresomes form.”

The studies open the door to solving a big puzzle concerning AMR which is how some bacteria called ‘persisters’ can hibernate during stress but then come back to life once the stress is removed.

An international team of researchers from multiple disciplines including biophysics and microbiology contributed to the research.

The team developed microbiology methods on range of bacteria to put advanced dye tags onto proteins and RNA while the bacteria were still alive, acting as single molecule light bulbs which could be tracked using state-of-the-art biophysics in laser-based fluorescence microscopes.

Prof Leake said: “The UK is really leading the way in discovery transformative approaches at the interface between the physical and life sciences such as this, especially emerging centres of excellence in the North East of England with York showing promise behind leading biophysics research institutes such as at Durham University.

“New scientific findings such as ours help us to understand at the level of single cells and single molecules how bacteria can side-step our immune defences and antibiotics – it lifts the hood on combating the global threat from superbugs, since if we can understand how aggresomes form we stand then a chance of working out clever ways to destroy them.”

About this research

Macrophage-derived reactive oxygen species promote Salmonella aggresome formation contributing to bacterial antibiotic persistence is published in the journal iMeta. Aggresomes protect mRNA under stress in Escherichia coli is published in the journal Nature Microbiology. The study was funded by the Engineering and Physical Sciences Research Council, the National Science Fund for Distinguished Young Scholars, Beijing Natural Science Foundation, the China Postdoctoral Science Foundation and the Ministry of Science and Technology of the Republic of China