COGNISEPLANCTOMYCES · Construction of a Genetic System for Planctomycetes

Construction of a genetic system for planctomycetes

Starting with the first clinical use of penicillin in 1942, bioactive molecules produced by fungi, bacteria and plants revolutionised medical treatment of infectious diseases. It has become disturbingly evident in recent decades that the combined misuse and overuse of antibiotics has resulted in a dramatic increase in the resistance of pathogenic microbes to known compounds. Consequently, only 70 years after the first antibiotic treatment, we again face the spectre of incurable bacterial infections, now due to multidrug resistant pathogens. Concurrently, lack of financial incentive has discouraged efforts by pharmaceutical companies to discover new antibiotics. As a result, only two new classes of antibiotics have been brought to market in the past 30 years. It is consequently widely acknowledged that there is an urgent need for new antibiotics, thus for novel lead structures to guide their development. Naturally-occurring secondary metabolites have been a rich source of new lead structures that, in turn, were modified to yield multiple compounds for potential drug development. Since the low-hanging fruits have already been harvested, finding novel lead structures today calls for new approaches. To identify novel lead structures or modes of action, the bioactive molecule repertoire of more, and more diverse, organisms need to be explored. To meet these demands the project COGNISEPLANCTOMYCES focused on such novel, barely studied bacteria as sources for antibiotics: Planctomycetes. The relative slow growing planctomyceteal species dominate biofilms in attractive habitats in terms of nutrition supply, such as surfaces of kelp water plants. How they can outcompete their faster growing heterotrophic competitors has been enigmatic, but the production of antibiotics was postulated as possible explanation. Once the first planctomycetal genomes had been sequenced, preliminary bioinformatics analysis pointed towards the production of unusual secondary metabolites by Planctomycetes. However, before in depth investigation of their antibiotic production ability could begin, a model organism and genetic tools were required. Thus, finding the appropriate planctomycetal model organism and making it genetically approachable was the main objective of COGNISEPLANCTOMYCES. In addition, bioinformatic analysis was performed to further elucidate the secondary metabolite production capacity of recently sequenced planctomycetal strains. Such analysis revealed that Planctomycetes indeed produce novel secondary metabolites that might be of great interest for further investigations. In addition, Planctomyces limnophilus was found to be an appropriate model organism and genetic tools for its manipulation were developed as proposed. All findings were made available to the public and a list of publications and further details can be found at the website http://www.jogler.de. This website demonstrates the successful development of the funded project into a new research group at the Leibniz Institute DSMZ in Braunschweig, Germany.

Data: CORDIS, © European Union