Lugdunin:

An antibiotic from the human nose shapes the microbiome

Departments of Infection Biology and Microbial Bioactive Compounds (IMIT) and Department of Organic Chemistry

Multi-resistant pathogens like Staphylococcus aureus spread in alarming rates worldwide. New sources for drug discovery are required and our own microbiome might be such a source. The human nose represents the natural habitat of S. aureus and nasal carriage predisposes individuals to infections with this pathogen. Nasal decolonization of S. aureus with mupirocin is a common strategy for infection prevention. However, resistance rates against mupirocin are steadily increasing demanding alternative decolonization strategies.

The nasal cavity represents a nutrient scarce environment suggesting fierce competition between bacterial species and potential production of inhibitory compounds. While screening nasal bacterial isolates for antimicrobial activities, we discovered Staphylococcus lugdunensis, to produce lugdunin, a novel antibiotic with potent activity against a broad spectrum of bacteria including multi-resistant strains.

Spontaneous resistance mutations against lugdunin did not occur under long-term selective pressure and a skin infection in mice was successfully treated. Nasal instillation of lugdunin-producing S. lugdunensis in rodents significantly reduced S. aureus and a clinical study with high- risk patients demonstrated that carriers of S. lugdunensis have a six-fold reduced risk of simultaneous S. aureus colonization.

Selected publications on nasal nutrient limitations, nasal antimicrobial activities and lugdunin:

Zipperer, A., Konnerth, M.C., Laux, C., Berscheid, A., Janek, D., Weidenmaier, C., Burian, M., Schilling, N.A., Slavetinsky, C., Marschal, M., Willmann, M., Kalbacher, H., Schittek, B., Brötz-Oesterhelt, H., Grond, S., Peschel, A., Krismer, B. 2016. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 535, 511-516 doi:10.1038/nature18634

Janek, D., Zipperer, A., Kulik, A., Krismer, B., Peschel, A. 2016. High frequency and diversity of antimicrobial activities produced by nasal Staphylococcus strains against bacterial competitors. PLOS Pathogens, doi: 10.1371/journal.ppat.1005812 doi:10.1371/journal.ppat.1005812

Krismer, B., Liebeke, M., Janek, D., Nega, M., Rautenberg, M., Hornig, G., Unger, C., Weidenmaier, C., Lalk, M., Peschel, A. 2014. Nutrient limitation governs Staphylcoccus aureus metabolism and niche adaption in the human nose. PLOS Pathogens, doi:10.1371/journal.ppat.1003862