German scientists dig into human noses, discover novel antibiotic

It’s not polite to pick your nose, but German scientists have dug deep into human noses to discover – for the first time – a molecule named epifadin produced by specific bacteria in the nose that has an antibiotic effect. 

Produced from specific strains of the bacterial species Staphylococcus epidermidis, it’s the first example of a class of previously unknown antimicrobial compounds that kills pathogenic microorganisms and could be used as a lead structure for the development of novel antibiotics.

Strains that produce epifadin can also be isolated on the surface of the skin. The human nose, skin, and intestine are colonized by both benign and pathogenic bacteria. These microorganisms live together in what are called microbiomes. If the microbiome becomes unbalanced, pathogens can increase, and we become ill. 

The occurs naturally in the dermal and nasal microbiomes of almost all humans. Epifadin works not only against the bacteria that are locally in competition with Staphylococcus epidermidis; it is also effective against bacteria from other habitats such as the intestine and certain fungi. 

The researchers found that it is especially effective against the potential pathogen Staphylococcus aureus, a hospital-acquired infection that is particularly dangerous in antibiotic-resistant form (MRSA).

Antagonistic bacterial interactions often rely on antimicrobial protein chains that attack only a narrow range of target bacteria, but antimicrobials with broader activity could be better. Seven years ago, the same working group headed by Dr. Bernhard Krismer and Prof. Andreas Peschel together with Prof. Stephanie Grond and Prof. Heike Brötz-Oesterhelt at the University of Tübingen discovered an unknown antibiotic substance with a unique structure that they called Lugdunin. Epifadin is now the second discovery of this kind that this working group has made in the human microbiome.

Epifadin is the second discovery of this kind

In experiments, the active substance epifadin reliably killed the pathogen Staphylococcus aureus, destroying hostile bacterial cells by damaging their cell membrane. The chemical structure of epifadin is extremely unstable, and the substance is active for only a few hours, so epifadin has a mainly local effect. This reduces the likelihood of collateral damage to the microbiome that is common with current treatments with broad-spectrum antibiotics. 

The team said that more research is needed to discover whether epifadin or its derivates can be used for therapy. For instance, epifadin-producing Staphylococcus epidermidis might be colonized in the nasal mucosa and other places on our skin and thereby suppress the growth of pathogens such as Staphylococcus aureus. This could prevent bacterial infections – using natural means that our bodies already have.

Researchers from the Cluster of Excellence “Controlling Microbes to Fight Infections” CMFI at the University of Tübingen tracked the active substance and its structure down ten years ago, when they first managed to isolate the strain. Complex natural substances such as epifadin are formed by microorganisms from single components using enzymes – this is called ‘biosynthesis’. Initial attempts to reproduce this biosynthesis indicated early on that it was an extremely novel molecule. It took several years of close cooperation on chemical analysis and synthesis at the University of Tübingen’s Institute of Organic Chemistry before they succeeded in accumulating and storing the active substance in a way that enabled complete isolation of the pure substance.

The new study has just been published in the prestigious journal Nature Microbiology under the title “Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus.” 

Study leader Dr. Bernhard Krismer from the Interfaculty Institute of Microbiology and Infection Medicine at Tübingen recalled: “The data from the lab was extremely interesting, but difficult to interpret because of the instability. Despite the difficulties, I thought it was still worth continuing research into it. Tenacity and a high tolerance of frustration have finally led to success.”

Microbiology Prof. Andreas Peschel added: “The development of new antibiotics has stagnated for decades. But we need them more than ever because in recent years, we’ve registered a rapid rise in multiresistant bugs around the world. It is hard to get control of these infections, and our reserve antibiotics no longer have such a strong effect. We urgently need new active substances and treatment methods.”

Follow-up studies will investigate the effect of the active substance on the basis of its structure. Here too, the perishability of epifadin makes extensive chemical and biological analysis more difficult, so they will begin by using chemical synthesis in the laboratory to produce artificial molecules with a similar structure and antimicrobial effect as epifadin that are stable and easier to work with.”