Novel Antibiotic Found in Human Nose: Researchers Uncover Promising Active Ingredient

Researchers at the University of Tübingen have discovered a novel antibiotic agent in the human nose that could be used against pathogenic bacteria. The molecule called epifadin is produced by certain bacterial strains of the species Staphylococcus epidermidis , which occur on the mucous membrane of the inner wall of the nose. In addition, epifadin-producing strains could also be isolated from the skin surface. Epifadin creates a new, previously unknown class of microorganism-killing agents that could be used as a lead structure for the development of novel antibiotics.

The human nose, skin and intestines are colonized by both benign and pathogenic bacteria. These microorganisms live together in so-called microbiomes. If the microbiome is out of balance, pathogens can multiply and we become ill. The bacterium Staphylococcus epidermidis occurs naturally in the skin and nasal microbiome of almost all people. The newly identified strain probably produces the active ingredient epifadin to assert itself against competing microorganisms. Epifadin is not only effective against those bacteria that are in local competition with Staphylococcus epidermidis . Epifadin is also effective against bacteria from other habitats such as the intestines and against certain fungi. Particularly good effectiveness was found against the potential pathogen Staphylococcus aureus , which is also known as a hospital germ and is particularly dangerous when it occurs as an antibiotic-resistant form (MRSA).

Already in 2016, the same working groups of Dr. Bernhard Krismer and Prof. Dr. Andreas Peschel, together with professors Stephanie Grond and Heike Brötz-Oesterhelt at the University of Tübingen, developed an unknown antibiotic active ingredient with a unique structure – the so-called lugdunin. Epifadin is now the second discovery of this type by these groups to be made in the human microbiome.

In the experiment, the active ingredient Epifadin kills the pathogen Staphylococcus aureus very reliably. The active ingredient damages the cell membrane of hostile bacterial cells, which destroys them. The chemical structure of Epifadin is highly unstable and the active ingredient is only active for a few hours. This means that Epifadin has a primarily local effect and collateral damage to the microbiome, as with current treatments with broad-spectrum antibiotics, is less likely. Only future research will show whether Epifadin or its derivatives can be used for therapy. For example, it would be conceivable to specifically colonize epifadin-producing Staphylococcus epidermidis in the nasal mucosa and other places on our skin and thus suppress the growth of pathogens such as Staphylococcus aureus . In this way, bacterial infections could be prevented – with natural remedies that our bodies already have.

Researchers from the Cluster of Excellence “Controlling Microbes to Fight Infections” CMFI at the University of Tübingen discovered the active ingredient and its structure ten years ago when they were able to isolate the producing strain for the first time. Complex natural products such as epifadin are formed by microorganisms using enzymes from individual building blocks – called “biosynthesis”. Initial attempts to understand this biosynthesis had already pointed to a completely new molecule. Only after several years of close collaboration with the chemical analysis and synthesis department of organic chemistry at the University of Tübingen did they succeed in enriching and storing the active ingredient in a way that enabled complete isolation of the pure substance.

Study leader Bernhard Krismer from the Interfaculty Institute for Microbiology and Infection Medicine (IMIT) remembers: “The data from the laboratory were very interesting, but difficult to interpret because of the instability. I felt that despite the difficulties, it was worth continuing to research. Persistence and a high tolerance for frustration ultimately led to success here.”

Andreas Peschel, Professor of Microbiology at the University of Tübingen and spokesman for the CMFI Cluster of Excellence, adds: “The development of new antibiotics has been stagnating for decades. But we need them more than ever, because we have seen a rapid increase in multi-resistant germs worldwide in recent years. These infections are difficult to control and our backup antibiotics no longer work as well. We urgently need new active ingredients and treatment methods.”

Follow-up studies will aim to draw conclusions about its effect from the structure of the active ingredient. Here too, the short shelf life of epifadin makes comprehensive chemical and biological analysis difficult. Therefore, molecules with a similar structure and antimicrobial effect to epifadin, which are more stable and easier to work with, should first be artificially produced in the laboratory using chemical synthesis.