New Antibiotic from a Detrimental Fungus

The causal agent of ash dieback may soon be providing us with beneficial substances

Nahaufnahme der Fruchtkörper des PilzesHans-Otto BaralClose-up of the fruiting body of the fungusFungi are extremely important for us human beings – both in a positive and in a negative sense. Some species are being used biotechnologically for the production of food, enzymes and antibiotics, whereas others are detrimental, causing great agricultural damage. However, as scientists from the Helmholtz Center for Infection Research (HZI) and from the Technische Universität Braunschweig have shown, it may be possible to attain substances that are beneficial for humanity from one of these pests. The scientists published their results in the journal Phytochemistry.

The causal agent of ash dieback, a tiny cup fungus with the scientific name, Hymenoscyphus pseudoalbidus, has recently caused serious disease of the common ash throughout all of Europe. To the best of our present knowledge, the pest came to Europe from Japan together with its natural host, the Mandshurian Ash, Fraxinus mandshurica.  In its native Asian country, the fungus is completely harmless. However, if the fungus infects the European ash, the trees die within just a few years. In some regions of eastern Europe, more than 90% of the ash trees have been killed, and the disease has already spread west as far as Spain and Ireland.

Leading scientists from throughout Europe, with financial support from the EU and assistance from the USA and Asia, formed the international research network, COST Action FP1103 „FRAXBACK“, to jointly attempt to find a method to control this dangerous invader. Experts in Braunschweig, who do research in the fields of biodiversity and natural products, are also attempting to unravel the causes of this dangerous disease.

An initially surprising discovery was made by the research groups of the HZI and the TU BS: The scientists isolated a novel antibiotic from the cultures of this fungal pathogen. Of note is the fact that it is particularly active against one certain bacterium.  „One of the strongest inhibitions was against a strain of the dangerous, pyogenic bacterium, Staphylococcus aureus. This so-called MRSA-bacterium has multiple antibiotic resistances “, said Marc Stadler, head of the Department “Microbial Drugs“ at the HZI. „These are already resistant to penicillin and other antibiotics that are presently on the market. “

„Hymenosetin“, as the new antibiotic was named, also inhibits human cell cultures and other microorganisms, and thus is not yet ready for pharmaceutical development and medical application. „In addition to the attempt to increase the effectiveness of the antibiotic, we are also trying to make it less toxic. And, we are attempting to develop a biotechnological process for mass production of hymenosetin“, said Stadler. 

In spite of its antibiotic activity, the scientists showed that hymenosetin neither inhibits germination of ash seeds, nor does it cause disease of the host leaves. It has already been shown that the fungus produces other substances that are toxic to the plant. „It could be that the antibiotic is not involved in the disease, but rather is a defensive weapon against other fungi and bacteria that also live within the plant tissue“, said Sandra Halecker, PhD candidate at the HZI und first author of the article. Scientists at the HZI and TU BS will attempt to test this hypothesis with basic ecological research approaches.

The new substance will also be made available to scientists of the German Center for Infection Research (DZIF) to study for other possible applications. Scientists of the HZI and TU participate in the DZIF, an initiative of the German Ministry for Education and Research (BMBF) to investigate disease pathogens.

The publication resulted from a co-operation between scientists of the HZI and the TU Braunschweig, including, in addition to the research group of Marc Stadler at the HZI, the groups of PD Dr. Barbara Schulz und PD Dr. Jeroen Dickschat, both from the TU BS.

One of the goals of the cooperation is to study the toxins that the fungal pest produces. Another goal of the scientists is to isolate endophytes, fungi that grow within plants without causing disease, from healthy ash trees. These might be natural antagonists of the fungal pest, “enemies” of the pathogen. They might eventually find application in biological control of the pathogen.

Original publication:

Sandra Halecker, Frank Surup, Eric Kuhnert, Kathrin I. Mohr, Nelson L. Brock, Jeroen S. Dickschat, Corina Junker, Barbara Schulz, Marc Stadler .Hymenosetin, a 3-decalinoyltetramic acid antibiotic from cultures of the ash dieback pathogen, Hymenoscyphus pseudoalbidus.Phytochemistry, 2014, DOI: 10.1016/j.phytochem.2014.01.018


More illustrations can be found here.  

The Microbial Drugs Department of the HZI is concerned with the investigation of microorganismally produced substances that can be medically exploited, such as for use as antibiotics. The team's primary focus is on a group of bacteria called myxobacteria.

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