Mining microbial resources for novel antifungal drug leads

Principal Investigator: Dr Jasmina Nikodinovic-Runic

The rising incidence of lifethreatening invasive fungal infections (FIs) and the development of resistant fungal strains are usually coupled with severe side effects and unsatisfactory therapeutic response of known antifungals. FIs have been marginalized for a long time, however, they recently came in focus as it became known that polymicrobial (fungi and bacteria) and drugresistant infections lead to around 25 000 deaths each year in the EU alone. Significant investments in basic research are thus needed to drive the discovery in the field of advanced antifungal therapy.

Secondary metabolites from the bacterial genus Streptomyces have been one of the major sources of novel drugs. Genetic analyses suggest that many novel molecules with potential therapeutic applications are still waiting to be discovered from these natural sources. Streptomyces usually contain more than 30 biosynthetic gene clusters, but only few metabolites might have been identified. Hence, applying advanced chemical screening coupled with targeted bioassay approaches and mining the genomic data is currently revolutionizing microbial natural products discovery and bringing its potential as source for novel drugs into focus again. In this project, we will – for the first time – screen an untapped Streptomycetes culture collection gathered over 20 years within LMMGE (IMGGE) from variety of sources and ecological niches. Identification of novel antifungal lead molecules will be achieved through rationalized bioassay guided screens targeting complex fungal quorum sensing and virulence (NikodinovicRunic, IMGGE) coupled with advanced isolation and chemical analysis techniques (Gulder, TUM). The shared goal of the project is the exploitation of untapped microbial resources of the Serbian partner in an integrated and complementary manner to discover new antifungal drugs. This work will lay the foundation for a planned long term collaboration of the partnering laboratories in the field of natural product discovery, characterization and development.