Researchers gain ground on elusive antibiotic resistance

Dan Andersson, a professor of medical bacteriology, has been researching bacterial evolution and antibiotic resistance for more than 30 years. He has now been awarded the 2026 Olof Rudbeck Prize “for his outstanding studies of bacterial evolution and its role in antibiotic resistance”.

The prize is awarded annually by Upsala Läkareförening for outstanding achievements in basic research that have had a significant clinical impact.

Dan Andersson was very surprised when he received the news.

“It was unexpected, I must say, but really thrilling. The fact that the prize is awarded by the Upsala Läkareförening medical society makes it feel extra special, given that I’m not a doctor and do not have that background.”

An interest in marine biology

It was far from a foregone conclusion that Dan Andersson would devote his research career to bacteria. When he began his studies at Uppsala University, his aim was to become a marine biologist.

“I decided that when I was fifteen, as I was into recreational diving.”
He studied chemistry and green biology, until a course was cancelled. The director of studies suggested he take a course in microbiology instead.

“After that course, everything else took a back seat. I completed my PhD in molecular biology and then started out in genetics as a postdoc. That’s when I realised this was my calling. I then moved on to evolutionary biology, and we eventually began using antibiotic resistance as a system for studying evolutionary processes.”

EU project on heteroresistance

Since then, bacterial genetics and evolution have been a constant theme in his research. From 1994 to 2004, he worked at the Swedish Institute for Infectious Disease Control. It was then that he began to focus on more applied infection research and antibiotic resistance. He was later appointed to a professorship in Uppsala and continued to combine basic research with applied research on antibiotic resistance.

This autumn, he is launching a five-year project, funded by the European Research Council (ERC), into the mechanisms behind so-called heteroresistance. Normally, a bacterium is either susceptible or resistant. Heteroresistance means that the majority of cells in a bacterial population are susceptible to antibiotics, while a small fraction are resistant.

“It could be one cell in a million, and this is not something that can be detected using standard methods,” explains Dan Andersson.

Difficult to diagnose

Previous research studies by the group show that heteroresistance is difficult to detect using current diagnostic methods. Another study shows that it increases mortality as a result of treatment failure. More research is needed here, as well as new diagnostic methods, according to Dan Andersson.

“We are trying to understand a form of resistance that essentially comes and goes. It is genetically interesting, from how the mechanism arises to how it affects treatment.”

Moreover, the resistance can come and go rapidly through changes in the number of copies of certain resistance genes. This creates a blind spot in several ways.

“Not only do we miss this and fail to understand why the treatment isn’t working, but we also tend to underestimate how common it is, because we lack the methods to detect it,” says Dan Andersson.

Developing new methods

Together with Maria Tenje, a professor of microsystems technology, he is developing entirely new methods for detecting heteroresistance. They are using microfluidics – essentially tiny laboratories on a chip – where patient samples and antibiotics are added in droplets. As soon as the bacteria grow, a reaction occurs, enabling heteroresistant bacteria to be identified quickly.

“We have developed a method to detect these small populations consisting of just a few cells Now we have a method where we can detect one in ten million that is resistant.

To ensure the research benefits more people, Maria Tenje and Dan Andersson have jointly founded the company Singular Diagnostics.
“We are in a development phase and have completed the fundamental research. Our next step is to build an instrument, test it in a hospital laboratory and see if it works. So now it’s a combination of engineering and working in a clinical environment.”

Basic research and clinical benefit

Basic research and clinical benefit are closer to one another than one might think, according to Dan Andersson.

“We would not have been able to develop these methods if basic research had not enabled us to understand the mechanisms and know what to look for.”

The new ERC project is not focused on developing new diagnostic methods. Dan Andersson and his colleagues will instead return to the fundamental questions of how heteroresistance arises and functions.

“It will be pure basic research. At the same time I believe that what we find will have clinical relevance. However, that is not the focus of this project.”

No plans to scale back

In his research, he enjoys working with younger researchers, such as PhD students and postdocs. He likes to see them grow and develop.

“I feel I’ve succeeded when they tell me the way things are. When they’ve become the specialists. But the best thing about research is the excitement – doing something that no one else has done. We have no idea what results we will get and don’t actually know where we will end up.”

With a five-year ERC project ahead of him, he has no plans to scale back, but has plenty of discoveries left to make with his colleagues over the coming years.

“The most enjoyable phase is the start-up phase of a project. That is when everything is possible, all the opportunities are there. It is when you start getting results and things start to get tricky that things become more complicated. At that point, you just have to keep working at it, not lose sight of the goal and keep trying,” says Dan Andersson.

Annica Hulth