Battle of the bacteria in our noses

Therapy Breakthroughs 15. feb 2024 2 min Group Leader Bernhard Krismer Written by Kristian Sjøgren

Bacteria are constantly at war in our noses, using various substances to influence or even kill each other. Now researchers have identified which bacteria are especially skilled at combatting Staphylococcus aureus. The discovery could lead to new types of treatment.

Our noses are full of different bacteria, some desirable and some undesirable.

The undesirable bacteria include S. aureus, permanently colonising the noses of about 20% of the global population and sporadically about 50%.

S. aureus is not an undesirable resident of the nose because of any damage it does there but because it increases the risk of serious infections elsewhere, including blood poisoning.

A new study now reveals that several natural bacterial enemies in the nasal passages are really good at combatting S. aureus.

The discovery may lead to new ways of combatting S. aureus and the accompanying risk of harmful infections.

“As biologists, we aim to develop any bacteria that effectively eliminate S. aureus and use them to combat such pathogens. If we can get these beneficial bacteria to colonise the nose, people will probably be protected against S. aureus and the accompanying risk of harmful infections for many years,” explains a researcher behind the study, Bernhard Krismer, Group Leader, Department of Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Germany.

The research has been published in Nature Microbiology.

Fifteen years of research

The quest to discover why S. aureus colonises many noses but not others began 15 years ago. People’s diet? Their genetics? Many studies showed that neither is the cause.

However, in a new series of studies, the researchers aimed to investigate whether bacterial interactions could be the explanation, with some bacteria being associated with the absence of S. aureus because they kill or outcompete S. aureus.

The researchers collected nearly 100 bacterial strains from the noses of healthy volunteers and isolated two that effectively kill S. aureus.

First, they identified Staphylococcus lugdunensis, which produces an active antimicrobial peptide called lugdunin.

“People whose noses are colonised with S. lugdunensis have one sixth the risk of having S. aureus. We published that result in Nature in 2016,” says Bernhard Krismer.

The other strain that can eliminate S. aureus is Staphylococcus epidermidis IVK83.

In the new study, the researchers show that this produces a new antimicrobial small molecule called epifadin that can also combat S. aureus.

“Epifadin-producing S. epidermidis, like our IVK83 strain appears to be quite rare. So far, only six isolates have been identified, four of which were in Tübingen, where the study was carried out,” explains Bernhard Krismer.

Epifadin as medicine?

Thinking that epifadin could be used to combat S. aureus is reasonable, but this is not that easy.

The further research on epifadin showed that it is very potent at fighting S. aureus but also very unstable. The researchers therefore failed many times to produce it in the laboratory.

Ultimately, however, the researchers purified it and characterised its structure.

They have therefore determined the structure of epifadin, showing that it very effectively eliminates S. aureus but also why it is so unstable.

“Light and probably oxygen rapidly degrade epifadin’s chemical structure. Trying to produce it as a drug to combat S. aureus is therefore a huge challenge,” explains Bernhard Krismer.

Using bacteria as medicine

Bernhard Krismer sees another possibility of using the discovery to combat S. aureus.

Rather than giving epifadin to people with chronic S. aureus colonisation, the researchers instead envision using S. epidermis IVK83 as a probiotic to ensure that the nose does not become colonised with S. aureus.

The researchers’ unpublished data for S. lugdunensis show that such natural colonisation with beneficial bacteria can keep S. aureus at bay for several years.

“This constantly protects people against S. aureus. Unfortunately, getting a treatment approved that involves colonising a person with bacteria will be very difficult, even though the bacteria will have a beneficial effect,” concludes Bernhard Krismer.

Bernhard Krismer therefore also recognises that the discovery may not end up as medicine, his ideal solution, but that chemists will instead have to determine how to make epifadin more stable while maintaining its ability to kill bacteria.

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