Active substance against resistant bacteria
16 June 2016
UniCat professor acquires new major project for the development of novel antibacterial substances
The situation could not be more contradictory: On the one hand, multi-resistant bacterial strains are on the rise, leading to the death of 25,000 patients infected with multi-resistant bacteria in Europe annually according to an estimate of the European Centre for Disease Prevention and Control (ECDC). In Germany, the number of estimated fatalities lies between 7,500 and 15,000 cases annually. On the other hand, the development of novel antibiotics has dropped since the 1970s. “We are lacking new classes of antibiotics substances, which can be used effectively against disease-causing bacteria. In addition, the pharmaceutical industry has largely retreated from antibiotics research and development,” says Prof. Roderich Süssmuth. He is Chair of Biological Chemistry at the TU Berlin and is active in the UniCat Research Areas D4 and E4.
Roderich Süssmuth has dedicated himself to the discovery of new active substances, especially antibiotics. It is one of the most important research areas of his working group. Research in this area is to be intensified with his new project “AlbiPharm”. The aim is to optimize the effectiveness of the antibiotics agent albicidin, to test it, and to prepare it as an active substance in a drug.
Albicidin was discovered in 1985 in the pathogenic bacterium Xanthomonas albilineans, which infests sugar cane plants. Roderich Süssmuth’s working group in collaboration with the French scientists of the CIRAD Institute in Montpellier uncovered the structure of the metabolite albicidin published 2015 in Nature Chemical Biology. The newly acquired project “AlbiPharm” will thus form the basis of the characterization of the structure of albicidin.
A particular feature of albicidin is its high efficacy against difficult to combat Gram-negative bacteria. These bacteria include coliform bacteria (Escherichia coli), Salmonella, Shigella, Klebsiella, Legionella, Pseudomonas, and Streptobacillus moniliformis, pathogens of the so-called rat bite fever.
“A focus of today’s antibiotics research must be the control of Gram-negative bacteria. Since in regard to the reservoir of agents against these germs, the pipeline is practically empty,” says Roderich Süssmuth. From a medical point of view, it is thus high time that research is intensified.
The molecular target of albicidin is gyrase, a vital enzyme for bacteria. It serves to wind up DNA during cell division. A special advantage is that gyrase inhibitors such as fluorchinolones, which are currently available on the market and have saved millions of lives, are especially efficient antibiotics. However, the amounts of albicidin that can be isolated from the bacterium are too low for additional optimization, and albicidin is now produced synthetically. The chemical synthesis is a protected patent of the TU Berlin.
In addition to synthetic access, which allows the relatively simple and cost-effective production of the agent, structural variations that improve the pharmaceutical properties of albicidin can also be carried out.
As interdisciplinary team of chemists, biochemists, and engineers, Prof Süssmuth’s group is working on the integration of chemical modifications within the basic structure. This is followed by an investigation of these newly synthesized derivatives in regard to their range of effectiveness on different strains of bacteria and their special pharmacological characteristics.
The aim of the project “AlbiPharm” is to develop a pharmaceutically active agent based on albicidin which is optimized for further research in animal models. This is to lay the foundation for the development of a new drug to be effectively used against multi-resistant bacteria.
“AlbiPharm” will be funded as part of the VIP measure of the Federal Ministry of Education and Research with a total of 1.6 million euros for the next three years.
In 2015 the Federal Ministry of Education and Research refreshed the tried and tested VIP measure: The innovative potential of research results is to be systematically verified through validation, and potential areas of application are to be developed.
Technological and societal innovations are equally addressed. Prerequisites for funding include the involvement of innovation mentors and potentially additional actors with experience in successful innovation processes. This is to ensure that funded projects are oriented towards subsequent commercialization and societal relevance.
Further information is gladly provided by:
Prof. Dr. Roderich Süssmuth
Chair of Biological Chemistry
Phone: +49 (0) 30 314-78774