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The abatement of phytopathological fungi

In the past, fungal infestation of agricultural crops has been known to affect the fate of entire nations, and nowadays it still continues to pose a threat to the world’s food supply. There is huge need for the development of new environmentally friendly agricultural fungicides, as fungi are fast becoming resistant to standard fungicides. Scientists are concentrating on the use of fungus-derived natural substances as the specific targets of fungicides in the metabolism of the fungi.

Every year, fungal infections lead to agricultural damage accounting for many billions of euros. Fungal infections have determined the fate of entire nations. One disastrous example is the destruction of the potato harvest in Ireland in 1844/45 by water mould Phytophthora infestans (which causes a serious potato disease known as potato blight), believed to have been imported from Mexico as hidden cargo. The destruction of the potato harvest led to a major famine, causing the death of around one million people. Two million people emigrated to the USA and Australia. The Irish population has still not returned to pre-famine levels. While the Church described the failure of the harvest as God’s punishment for people’s past extravagance, and one particular clergyman blamed the steam engines that belted across the island at speeds reaching 30 km/h, sending harmful electrical impulses onto the land, it was another clergyman, the English amateur researcher Miles Berkeley, who investigated the fungal threads of infected potato plants under the microscope. Berkeley was the first to describe the causes of potato blight. His findings were roundly rejected at the time. It was 15 years before the German plant pathologist Anton de Bary confirmed Berkeley’s observations and provided evidence for the fact that the fungus spread from plant to plant through tiny spores.

Hopes and disappointments in the abatement of potato blight

Potato blight, caused by Phytophthora infestans © Syngenta

Ireland was not the only country to face such a catastrophe. Germany experienced similar losses in its potato harvest in 1917 and 1918. Some of the remaining living witnesses can still recall the horror of the so-called "swede winter" during WWI. The discovery of a Phytophthora-resistant wild potato variety in Mexico, whose resistance genes were crossed into almost all European potato varieties, led to hopes that a victory over the pathogen was not far off. The chemical industry also developed fungicides for the treatment of potatoes against the mould fungus.

But even now the battle is still far from being won. Phytophthora is still regarded as one of the most dangerous fungi for agriculture.

According to the latest findings, Phytophthora is not a true fungus, but a representative of oomycetes. Together with brown algae and diatoms and a handful other algae, Phytophthora is classified as heterokont or stramenopile. Oomycetes differ from fungi in that they have flagellar zoospores and have a cellulose rather than a chitin cell wall. Oomycetes also include other greatly feared plant pathogens, such as Peronospora and Plasmopara viticola (downy mildew of grapevines). Powdery mildew (different species of the Erysiphaceae family) belongs to the ascomycetes, i.e. true fungi.

Besides potatoes, P. infestans also infests tomatoes (tomato late blight) and a number of other plants. It is estimated that P. infestans infections account for about 20 per cent of harvest losses worldwide.

All the strategies used to combat the fungus have led to the fungus developing new resistances. In the mid-1980s, new aggressive Phytophthora strains appeared in Europe as hidden cargo from Mexico. These newly introduced fungi reproduced sexually, which led to a further increase in their variability. Prior to the arrival of this fungus, no sexually reproducing Phytophthora strain had been known in Europe.

Promising genetic engineering approaches were put in place: Researchers at the Max Planck Institute for Plant Breeding Research developed a complex two-component system in which the ribonuclease (RNase) gene of a soil bacterium was controlled by the promoter of a pathogen defence gene in potatoes. The fungal infection activated the RNAse gene; the resulting RNAse then led to the destruction of the infected cell. However, it was not possible to continue the BMBF-approved and funded safety research field trials after opponents of genetic engineering destroyed the test field and its plants. Therefore, it is once again up to the chemical industry to come up with abatement strategies through the development of new fungicides and combination compounds to counteract the development of fungal resistances.

Helminthosporium and Magnaporthe

Abatement measures do not just focus on potatoes. Fungal infestations also cause huge damage to other crops (wheat, rice and maize) that are the staple food for a large number of the world’s population. The ascomycete (sac fungus) Magnaporthe grisea, which causes rice blight, destroys about one fifth of the Eastern Asian rice harvest every year, amounting to what would have been sufficient food for around 60 million people. Another serious pathogen is the ascomycete Helminthosporium, which causes spot blotch in maize and other cereals. In the 1970s, the fungus caused major damage to the North American maize crop. At the end of the 1990s, the fungus was observed for the first time in maize cultivations on the Upper Rhine, and subsequently also in Rhineland-Palatinate, Hesse and Bavaria, where it caused serious economic damage. After 2003, the disease seemed to be on the wane, but over the last two years it is once again advancing in all German regions.

Such pests can occasionally also have some positive effects: at the start of 2008, a team of researchers at the German Cancer Research Centre in Heidelberg discovered in Helminthosporium carbonum a substance that is toxic to neuroblastoma cells. There is the possibility of developing a drug to combat this cancer which occurs mainly during childhood (see article entitled "Plant Pathogen Yields Substance to Fight Neuroblastoma").

Strobilurines – a success story

Strobilurus tenacellus © www.pilz-baden.ch

There were huge expectations placed on the potential chemical abatement of Helminthosporium and other phytopathogens generated by the new fungicide class of strobilurines. Strobilurines were discovered in the 1970s by Timm Anke, a professor of biotechnology at the University (now Technical University) of Karlsruhe since 1981, in the fungus Strobilurus tenacellus, but are also found in some other basidiomycetes. In order to increase their stability and increase their range of anti-fungal use, the natural strobilurines were chemically modified. The first fungicides entered the market in 1996, the same year in which Timm Anke was awarded the Karl-Heinz Beckurts Prize for his discovery. Nowadays, around 11 different strobilurine fungicides are sold by companies such as BASF, Bayer and Syngenta.

Strobilurine A © ibwf

Since they are basically non-toxic for animals and plants and can be degraded rapidly in soil, at the same time as specifically inhibiting the mitochondrial respiration of fungi, strobilurines were seen as the perfect fungicide, which generated world-wide sales of over a billion dollars. In the meantime, as expected, numerous fungi have developed resistances to strobilurines or azoles, therefore making it necessary to develop new fungicides.

The Institute of Biotechnology and Drug Research in Kaiserslautern

Prof. Dr. Timm Anke © University of Kaiserslautern

Prof. Timm Anke and his wife, Prof. Heidrun Anke, established the Institute of Biotechnology and Drug Research (IBWF) in 1998 on the basis of their successful discovery of strobilurines. Together with their staff and partners, Timm and Heidrun Anke have turned the IBWF into a unique competence centre of applied mycology. The institute, located on the campus of the Technical University of Kaiserslautern, has collected around 10,000 different strains of all the large taxonomic fungal groups around the world. This collection is used by microbiologists, biochemists, chemists and molecular biologists in the development of new biologically active substances and enzymes from fungi. More than 20 patents and 500 publications are evidence of the IBWF's successful work.

In a cooperative research approach, the scientists at the institute are currently investigating the infection-relevant differentiation in phytopathogenic fungi as a target for modern fungicides that do not impede the vegetative growth of soil-growing or mycorrhiza-associated fungi. An example of a differentiation process that is impeded by non-fungitoxic plant protectants during the pre-penetration phase (before the fungus is able to penetrate the host plant) is the biosynthesis of melanin in Magnaporthe grisea (see above).

The research on fungicides at the IBWF is not only of great importance for agriculture, but also for pharmacology and medicine. The discovery of galiellalacton, a metabolite of Galiella rufa, also signalled the discovery of the first inhibitor of the interleukin-6-mediated signalling pathway, which plays an important role in a broad range of inflammatory processes.

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