Optimising antibiotics by capturing bacteria

Scientists at the University of Zurich, supported by the Swiss National Science Foundation (SNSF), have developed molecules to detect and capture certain bacterial species, in the hope that their rapid identification will allow antibiotic treatments to be optimised. Their research has been published in the journal Communications Biology.

The discovery of antibiotics revolutionised medicine in the 20th century; however, the emergence of resistant bacteria has quickly become a new challenge. One key factor in tackling this issue is being able to pinpoint the bacteria causing an infection, enabling healthcare providers to use targeted and effective antibiotics and reduce the risk of new forms of resistance development.

“In the race between the evolution of resistant bacteria and the development of new antibiotics, we don’t stand a chance,” said study leader Markus Seeger, a biochemist at Zurich’s Institute of Medical Microbiology. “Bacteria have been at war with viruses for millions of years and are used to evolving to escape new dangers.”

The only solution is to use antibiotics efficiently and sparingly, thus preventing bacteria from being constantly exposed to residues or traces of antibiotics in their environment. This strategy requires medical diagnoses that are as fast and accurate as possible; however, traditional identification involves collecting bacteria from the patient and then growing them until there are enough to carry out detailed analyses — which can take up to 12 hours for some species — with analysis itself then taking another two hours. Seeger and his team are looking to speed up this process.

“Our idea is to detect certain bacteria more quickly, even in small numbers, by giving them specific colours,” Seeger said. “We aim to capture them directly in the blood to increase their density and analyse them more quickly.”

This approach does not deliver a conclusive diagnosis, but it means the presence of certain bacteria can be confirmed faster than using traditional methods. This time saving is especially valuable in cases of bloodstream infections, where waiting one or two days for detailed analyses may not be feasible.

Seeger’s team concentrated on detecting the bacteria Escherichia coli (E. coli), commonly linked to urinary tract infections and bloodstream infections. Resistance rates for this species of bacteria significantly increased in Switzerland between 2004 and 2024, rising fourfold for certain classes of antibiotics.

“Knowing whether an infection involves Escherichia coli or something else is already a good basis on which to make an initial decision about which treatment to administer,” Seeger said. In fact, the tools developed by his team would save around six hours of the 12 needed for traditional diagnostics.

Seeger and his team had to solve two problems to capture E. coli. On the one hand, they needed to find the right bait — so a specific element common to all E. coli bacteria. On the other hand, Seeger said he “underestimated the complexity of the jungle of sugars acting as a barrier around the bacteria”, which is so dense that few molecules can penetrate it.

The scientists opted to use miniature antibodies, known as nanobodies, whose small size allows them to pass easily between the sugar branches. They are also more stable than conventional antibodies, meaning they remain functional for longer periods at room temperature. This is a key element to obtain detection tools that can be transported and stored without having to worry about cold chains.

The team searched an international database and a register of bacteria detected in Swiss hospitals. By analysing the genome of the recorded E. coli-type bacteria, a protein was identified — OmpA — a specific form of which is found only in E. coli. The group subsequently developed nanobodies capable of detecting this version of OmpA in a targeted and effective way in over 90% of species members.

“To detect Escherichia coli, this works well,” Seeger said. “We can attach tiny colourant molecules to the nanobodies without significantly increasing their size.

“However, to capture the bacteria, we use larger magnetic beads, and they can’t penetrate the jungle of sugars that surrounds the bacteria,” Seeger added. So the scientists created a sort of fishing rod for their detection kit — a molecular thread that was developed to connect the nanobodies (the hook) to the magnetic beads blocked by the sugars (the handle).

“We now have a tool to detect and capture Escherichia coli,” Seeger said.

“The developed molecules are already being used in a partnership with the Zurich startup rqmicro, which provides tools to monitor water quality.

“I hope we can successfully implement it in clinical diagnostics.”

Image credit: iStock.com/Artur Plawgo