New study maps bacterial communication to fight MRSA infections

Imagine two people talking over a walkie-talkie set. Successful communication depends on them being tuned to the same frequency. If others try to communicate nearby, interference can occur, and important messages may be lost.

Something similar happens in the world of bacteria. Bacteria communicate on their own "frequencies" when, for example, they coordinate an attack on a host by infecting a wound. However, other bacterial species can disrupt this communication, which, in turn, weakens the ability to coordinate and attack.

Now, researchers from the University of Copenhagen have conducted the largest mapping to date of the frequencies – or signaling molecules – that Staphylococcus bacteria use to communicate.

Staphylococci are a family of bacteria that, among other places, live on our skin. One species, Staphylococcus aureus, also exists in antibiotic-resistant variants known as methicillin-resistant S. aureus (MRSA). MRSA strains are therefore more difficult to treat than regular staphylococci.

The researchers then used their new knowledge to effectively treat an MRSA infection.

With our mapping, we can identify which signaling molecules are most effective against MRSA. We found that a signal from another Staphylococcus variant, Staphylococcus simulans, was very potent against S. aureus. Originally, the signaling molecule was isolated from a bacterial strain from a cow, but it is also present on goats, horses and humans."

Christian Adam Olsen, professor at the Department of Drug Design and Pharmacology at the University of Copenhagen and one of the authors of the new study

The researchers tested, in a mouse model, whether the signaling molecule from S. simulans could also disrupt MRSA signals and prevent infection. It could.

"In the experiment, we showed that with a single dose of this signaling molecule, the mice could overcome an MRSA skin infection just as effectively as mice treated daily with an antibiotic ointment, which is a current option for treating staphylococcal skin infections," says postdoc Benjamin Svejdal Sereika-Bejder, who also contributed to the new study.

A new weapon against antibiotic resistance?

Antibiotic resistance is an increasing problem in society, which is why there is great interest in finding alternative treatments for bacterial infections. Therefore, the researchers also investigated whether bacteria would develop resistance towards treatment with the signaling molecule.

"No one has previously tested whether staphylococci develop resistance towards treatment with these signaling molecules, as we see with antibiotics. In our experiments, we observed that under laboratory conditions, the bacteria did not develop resistance even after 15 days. This is very promising but will require further testing in animal models," says postdoc Benjamin Svejdal Sereika-Bejder.

This alternative technique weakens the bacteria's ability to communicate effectively but does not kill them, as is the case with antibiotics. The bacteria are allowed to live but have a harder time coordinating an attack on the host's immune system.

"The explanation is likely that there is no evolutionary pressure on the bacteria to develop resistance, as they do not perceive the signaling molecules as being lethal to them. They are also encountering the signaling molecules from other bacteria in their natural environment," says Christian Adam Olsen.

Source:
Journal reference:

Gless, B. H., et al. (2025) Mapping of quorum sensing interaction network of commensal and pathogenic staphylococci. mBiodoi.org/10.1128/mbio.00967-25.

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