Microbial Drugs
The majority of the medically important antibiotic drugs are derived from secondary metabolites, which are produced by bacteria and filamentous fungi. Despite intensive world-wide efforts using alternative approaches, no other concept could so far surpass the historically successful strategy to exploit biologically active natural products as candidates for anti-infective drugs. The recently observed, increasing resistance of the human pathogens against antibiotics has prompted us to intensify our search for novel lead structures from microorganisms and fungi, which can be used as anti-infective drugs.
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Mycology
In the past, not only penicillins and cephalosporins, the discovery of which ushered in the era of modern antibacterial chemotherapy, but also other important active ingredients for use in other pharmaceutical indications were obtained from cultures of filamentous fungi.
Without the discovery of cyclosporine, modern therapies based on organ transplants would certainly not be possible to the extent that is practiced today. The statins (mevinolin, lovastatin), which are also originally obtained from mushrooms and from which highly potent cholesterol-lowering drugs are obtained, are still the most successful class of drugs ever. In recent years, other active ingredients from fungi such as pneumocandin derivatives (antimycotics) have been introduced onto the market. Emodepside is one of the most potent antiparasitic drugs used in veterinary medicine today. Incidentally, it is one of the few substances from endophytic microorganisms that has resulted in a marketed product to date. Only recently, Ibrexafungerp, a new antimycotic based on fungal endophytes, was approved for the treatment of fungal infections.
All of the aforementioned substances come from Ascomycota and their asexual stages, but many biologically active natural substances have also been discovered from cultures of Basidiomycota. The strobilurins are one of the most successful classes of fungicides in crop protection today, and the pleuromutilins are the latest antibacterial terpenoid antibiotics that have been approved for the treatment of infections in animal health and for the treatment of skin infections, as well as for the control of systemic lung infections in humans.
However, according to some estimates, only a very small percentage of the global biodiversity of fungi has so far been explored. Therefore, we are deliberately seeking for interesting, hitherto untapped fungal organisms, using taxonomy and chemical ecology as pre-selection criteria. For provision of new strains, we can rely on a global research network, which involves collaborations with some of the most renowned mycological research groups. Over the past years, we have obtained massive third party funding for joint research activities. We are also involved in academic exchange programs with partners from tropical countries that involves capacity building in the source countries. In addition, we are collaborating with citizen scientists who are helping us with their expertise.
Some examples for ongoing projects are listed below, and further information can be found in the provided links.
- Evaluation of new species of tropical mushroooms for production of novel anti-infectives
- Secondary metabolites and taxonomy of coprophilic fungi, with special emphasis on the ascomycete order Sordariales
Story: New drugs from fungi
HZI researchers traveled to Yaoundé, Cameroon, for a workshop on the collection, culture and identification of fungal strains. A new research hub will strengthen natural product research in fungi in the country. [read more]
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