During the Middle Ages, the mysterious disease that was manifested in horrible visionary hallucinations, seizures and convulsions, burning pain, chancre and gangrene of the limbs, was called Saint Anthony’s Fire. Today we already know that these symptoms of poisoning, called ergotism, were, in fact, caused by the consumption of cereals infected with parasitic fungi. According to contemporary legends, those who wanted to be cured had to make a pilgrimage to the relics of Saint Anthony or to his grave. However, it was rather the activities of the monks of the Order of Saint Anthony that really helped, as these monks were particularly successful at treating this ailment. What they actually did was they simply gave grains and flour to the inhabitants that was not infected.
“Claviceps paspali is a parasitic fungus that infects various types of grain crop, and then tries to overwinter on the plants. For this part of its lifecycle, it forms a hard and compact mass (sclerotium), the popular Hungarian name for which is varjúköröm [verbatim: crow’s nails], which contains spores of fungi and high concentrations of toxins. One type of these toxins is known for contracting muscles, including the ones in veins, for which reason it is used even today for haemostasis,” explains Professor István Molnár, a researcher at University of Arizona Natural Products Center in the United States, who works as a guest professor at Debreceni Egyetem Természettudományi és Technológiai Karának Biotechnológiai és Mikrobiológiai Tanszéke [Department of Microbiology and Biotechnology of the Faculty of Science and Technology of the University of Debrecen] with the support of the Biotechnology Program of Felsőoktatási Intézményi Kiválósági Program [verbatim: Institutional Excellence Program in Higher Education].
According to Professor Molnár, these toxins had been used a long time ago in ancient China to facilitate childbirth especially because of their effect of contracting smooth muscles, whereas today they are mostly applied for the treatment of migraine and for alleviating the symptoms of Parkinson”s disease.
“We extract these toxins from spurred rye to modify them chemically in order to strengthen their positive effects and to diminish the negative ones. We can achieve this through establishing mutations, for which we use a variety of methods to implant DNS sequences into the genetic stock of the fungi. However, this is not always successful, which is why we are working on developing new technologies for it together with the researchers of TEVA Pharmaceutics in Debrecen. In our research, we have adapted a new procedure to this fungus for a different type of DNA insertion with the cooperation of Professor István Pócsi, the Head of the Department of Microbiology and Biotechnology. This new technology will open up the possibility of utilizing this industrially useful strain in pharmaceutics even more efficiently,” said Professor István Molnár.
In fact, the researchers have adapted a genetic transformation method that will switch off the production of useless or harmful components in the fungus, and this will contribute to superior productivity and a better safety profile for the starting material.
“Modern purifying technologies make it possible to get rid of harmful materials during the course of production, while it is much safer from the aspect of side effects and a lot cheaper from the aspect of production if the starting material does not contain that pollution,” said the professor.
István Molnár added that it would be possible in the future that these currently harmful alkaloid compounds would serve as raw material for medicine, because that was often the case when a compound with negative effects would be genetically modified to create different kinds of medicine, just like in the case of ergot or spurred rye.
Descriptions and the findings of the research project have been published in the prestigious scholarly periodical Applied Microbiology and Biotechnology and TAPI, the journal of TEVA Gyógyszergyár [TEVA Pharmaceutical Works], with which the University of Debrecen is in close research cooperation.
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