Swarm border with single cells (Sorangium cellulosum)
Most of the clinically-relevant antibiotics are of microbial origin or are derived from microbial drugs. Despite world-wide extensive efforts in the search for alternative sources of anti-infective drugs, the successful strategy of using microbial drug-principles to combat infectious diseases was never exceeded by other concepts. In light of the threatening upcoming resistance against established antibiotics and the appearance of new infections, the anti-infection research is challenged to reinforce the screening for improved drugs from the realm of the microorganisms.
By the ongoing efforts of the HZI (formerly known as GBF) myxobacteria (Order Myxococcales) have been established as very fruitful source of drugs with unique structures and novel mechanisms of action. For example, the antibiotic effect of sorangicin A is similar to that of the clinically applied rifampicin. With its powerful antifungal plant-protective action, soraphen A set a new standard and disclosed a new target for antifungal drugs, i.e. the actetyl CoA carboxylase. In clinical studies a HZI-born derivative of epothilon has proven especially useful as therapeutic for the treatment of drug-resistant cancer and thus will most likely be approved as chemotherapy soon.
The work group Microbial Drugs now comprises microbiologists, biotechnology experts, pharmacists and natural products chemists. The group has recently re-focused its working power to expand the search for improved antibiotics to rarely screened or new species of myxobacteria as well as other drug-producing bacteria. For this intensified utilization of biodiversity new isolation methods for bacteria are developed, in order to bring uncommon or even unknown species into culture for the screening. Additionally, genetic information about the producing organisms are elucidated and applied to exploit the genetic potential of these organisms for the expression of novel or modified drugs or to increase their production. A broad test spectrum (bacteria, fungi, yeasts, cell cultures, enzymes), including antibiotic-resistant strains, is used to recognize possible drug candidates. Chemically, the extracts are examined by analytic HPLC with UV and MS detection for new but also for known microbial products. New compounds are isolated and their structures are determined.
Simultaneously, the purified products are tested in diverse biological systems for their action and their mechanisms of action. Beyond that, the compounds are provided to intra-centre and external academic but also to industrial co-operation partners for specialized testing, e.g. against malaria and other parasitic tropical diseases. As a amelioration/amplification of infection-related natural product research, larger substance samples are produced biotechnologically, e.g. for chemical studies of the work group Medicinal Chemistry, the junior work group Structure and Function of Antibiotics or the department Chemical Biology. In order to transfer promising compounds into practical use the work group Microbial Drugs cooperates with industrial partners and provides the necessary amount of a drug for the first developmental steps by large-scale fermentation and purification.