Prof. Dr. Heike Brötz-Oesterhelt

University of Tübingen

Title: “Understanding the Mechanisms of Unconventional Antibiotics from a Holistic Perspective”

Abstract: There is an urgent need to discover unprecedented antibacterial mechanisms effective against multi-resistant bacterial pathogens. Secondary metabolites produced by bacteria and other microorganisms (‘natural products’) are a valuable source of new and inspiring antibacterial mechanisms, which are often multi-layered. Natural products produced by commensals from the human microbiome bear potential as decolonizing agents as they evolve on human surfaces and can have antibacterial activities. Also, uptake routes of antibacterial agents across the bacterial cell envelope are important, as they may or may not be prone to resistance development. The talk will showcase selected examples of antibacterial natural products with elaborate mechanisms, considering primary and secondary targets, polypharmacology and ecological context.

Literature: 

Berscheid A, Straetener J, Schilling NA, Ruppelt D, Konnerth MC, Schittek B, Krismer B, Peschel A, Steinem C, Grond S, Brötz-Oesterhelt H. The microbiome-derived antibacterial lugdunin acts as a cation ionophore in synergy with host peptides. mBio, doi: 10.1128/mbio.00578-24 (2024).

Lewis K, Lee R, Brötz-Oesterhelt H, Hiller S, Rodnina MV, Schneider T, Weingarth M, Wolgemuth I. Sophisticated natural products as antibiotics. Nature 632:39-49 (2024).

Torres Salazar BO, Dema T, Schilling NA, Janek D, Bornikoel J, Berscheid A, Elsherbini AMA, Krauss S, Jaag SJ, Lämmerhofer M, Li M, Alqahtani N, Horsburgh MJ, Weber T, Beltrán-Beleña JM, Brötz-Oesterhelt H, Grond S, Krismer B, Peschel A. Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus. Nat Microbiol, doi: 10.1038/s41564-023-01544-2 (2023).