Objectives
The increased life expectancy in developed countries is the great success story of antibiotics. However, the increasing global spread of antibacterial resistance presents a tremendous health threat and misguided decisions to reduce basic research have seriously limited the development of new antibiotic drugs.
The FOR 854 concept for antibiotic research is primarily biology-driven and integrates microbiological, biochemical, chemical and pharmaceutical research to study new antibiotic compounds and antibiotic mechanisms and targets. Through this synergestic approach, we identified several new novel antibiotic gene clusters by genome mining, studied biosynthesis reactions, characterized structures and activities of new compounds, and discovered a new treatment option for parasitic diseases by targeting bacterial endosymbionts. We characterized novel targets with novel mechanisms, the bacterial proteasome and riboswitches, and studied potential inhibitors. We analyzed the functional organization of cell wall biosynthesis and cell division and the mechanisms by which antibiotics disturb these processes.
In the next funding period we want to focus on the most promising compounds identified so far and continue genomic mining. Moreover, we want to improve our mechanistic understanding of drug activities in a cellular context for better design strategies and identification of new targets. The proposed research will provide deeper insights into fundamental biological processes associated with biosynthesis and activities of antibiotics. Together with intensive training of young scientists, this will broaden the basis for future development of innovative antibiotic drugs.
