Yeasts, such as Candida albicans, can cause obstinate skin diseases and are a serious health risk for patients with a compromised immune system. Scientists from the Helmholtz Centre for Infection Research (HZI) in Braunschweig and the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken recently discovered new substances that are active against this type of fungal infections. They report the two substances called pinensin A and B in the current issue of "Angewandte Chemie".
Scientists at the HZI are also actively searching for natural substances with, e.g., an antibiotic effect. The scientists often strike it rich when they investigate microorganisms from the soil. As was the case with the recently discovered pinensins: They are produced by Chitinophaga pinensis, a gram-negative soil bacterium, and belong to the group of the lantibiotics. This class of antibiotics was thus far produced in significant quantities only by gram-positive bacteria and has a very specific effect against other gram-positive cells. "Surely, the most prominent example of a lantibiotic is nisin. It is present in cheese rinds and is produced by lactic acid bacteria," says Dr Kathrin I. Mohr, who is a scientist in the "Microbial Agents" department of the HZI and, like Dr Carsten Volz, is one of the lead authors of the recently published study.
But pinensins have another special feature. "They are the first lantibiotics to be selectively effective against Fungi", says Mohr. "This means that we found new potential agents against fungal diseases such as candidiasis." There is an urgent need for antifungal agents of this kind since some of the available medications can have serious adverse effects. "The development of significant resistance has also been observed already, which necessitates the development of new fungicides," says Mohr.
The researchers discovered the pinensins in a so-called Screening. This involves the initial testing of microorganisms isolated from the environment for the production of substances with an antibiotic effect. If this is the case, the researchers attempt to isolate this substance. Once it is present in pure form it can be characterised exactly. This includes tests of any toxic effect on human cells. If the candidate agent is non-toxic, it can be further developed into a drug by industrial partners.
However, more work is required to get the pinensins to this point. In the course of this work, Kathrin Mohr and her colleagues are attempting to optimise the production of these substances in the laboratory: "Only substances that can be made available at a multi-grams scale have any prospect of success as candidate drugs. This is not the case yet," says Mohr. But this may change soon. Her co-author Volz already elucidated the synthetic pathway of the pinensins. Based on these insights, it may be possible to develop a simple procedure for the biotechnological production of these agents. Concurrently, the potential of the pinensins is being gauged in more detail. They might be useful not only as antifungal agents in medicine, but also as pesticides. "Since the level of resistance is on the rise, agriculture also has a permanent need for new fungicides," says Mohr.
Original publication:
K. I. Mohr, C. Volz, R. Jansen, V. Wray, J. Hoffmann, S. Bernecker, J. Wink, K. Gerth, M. Stadler, R. Müller. Pinensins: The first antimycotic lantibiotics. Angewandte Chemie, 2015, DOI:10.1002/ange.201500927.
