Azoles have many areas of application, and therefore work on azole resistance should be based on a One Health perspective. This means that we must see the important relationship between human health, animal health and the surrounding environment. Credit: Samantha Kim Pettersen, Norwegian Veterinary Institute
Fungi can cause disease in humans, animals, and plants. Every year, 1.5 million people die from fungal infections, and fungal attacks in food crops threaten food production. To protect ourselves, we have developed chemical agents in the form of medicines or pesticides that kill harmful fungi. The most effective remedies against fungal infections are a group of substances known collectively as azoles.
“It is important that the azoles we use have a good effect against pathogenic fungi,” says senior researcher Ida Skaar at the Norwegian Veterinary Institute.
Azoles are used really often – as medicine for humans and animals, to prevent fungal diseases in food crops and golf courses, to preserve wood, to prevent mildew in flower bulbs and silage. To grow and preserve ornamental plants. The list is long. Researchers are concerned about its repeated use because harmful fungi can develop resistance.
Little explored topic
Antibiotic resistance is a well-known issue that raises concerns among many people. In comparison, fungicide resistance is a little explored, but very relevant topic. The World Health Organization (WHO) has identified the Aspergillus fumigatus fungus, among other organisms, as a fungus that may pose a health threat in the future. A. fumigatus is a common fungus found everywhere, and it poses little threat to healthy people. For people with weakened immune systems, this can cause infections that need to be treated. In such cases it is important that the drug, which is usually based on azoles, is effective.
“A. fumigatus that is resistant to azoles is a growing global problem,” says Scarr.
“We don’t know what the situation is like in Norway, but with the wetter and warmer climate that we can probably expect in the future, the problem will become even bigger.
“Information about the situation in Norway is absolutely essential. We must be active and obtain the necessary knowledge before the problem becomes too serious. We must, among other things, know how much resistance we have, in what way Where fungi develop resistance, and in which environments resistance is likely to arise (so-called hotspots).
One Health: Everything is Connected
Skaar leads the Nevazole project which aims to map and understand the development of azole resistance in Norway. This knowledge is needed to make wise decisions to keep resistance levels as low as possible. This requires cooperation between different sectors.
“Azole resistance concerns many areas. So we must keep a One Health perspective in mind when dealing with it. This means we must acknowledge the important connection between human health, animal health and the surrounding environment. We must all “Applications need to be considered in the field of azoles, and examine hotspots for resistance development, and how resistance spreads further,” the senior researcher explained.
The World Health Organization (WHO) believes that the Aspergillus fumigatus fungus may pose a health threat in the future. For people with weakened immune systems, the fungus can cause infections that need to be treated. This is what the fungus looks like under an electron microscope. Credit: Jannik Wiik-Nielsen, Norwegian Veterinary Institute
Search for resistance in soil-dwelling fungi
One potential hotspot for resistance development is the use of azole-based pesticides in agriculture. In the project, NIBIO will work on this issue.
Andrea Fike is a researcher at NIBIO, working on fungal diseases in cereals. She explains how grain fields can be hotspots for resistance evolution:
“A. fumigatus is a soil-dwelling fungus that is also present in the field. In conventional agriculture, crops are sprayed against various fungal diseases, and many fungicides are based on azoles. Some fungicides end up in the soil. “And can affect A. fumigatus. In the same way that overuse of antibiotics can lead to resistance in bacteria, regular exposure to azoles can lead to resistance in A. fumigatus.”
In the project, researchers want to investigate whether they can find resistant A. fumigatus, which are sprayed with azole-based fungicides, and whether resistance development in plant pathogenic fungi and A. fumigatus.
“We are going to study two fungi that cause the leaf blotch diseases Septoria leaf blotch (Zymoseptoria tritici) and Septoria nodorum blotch (Parastagonospora nodorum). These diseases can cause significant damage to crops,” explains Fike.
Fike has been working on leaf spot diseases in cereals for 10-12 years. Over the years, they have not seen a worrying increase in resistance to fungicides. So far, Scarr’s research group has found resistant A. fumigatus has also not been found. However, this does not mean that we can rest on our achievements, quite the contrary.
Preventive action is important
“In Norway, we are very fortunate that we don’t have big problems with fungicide resistance in crops,” says Fike.
However, Scar showed a more resistant A. fumigatus, but he also believes the problem is relatively small in Norway. She adds, “But you don’t have to go further than Denmark before the situation becomes more serious.”
Both researchers stress the importance of focusing on this issue in Norway.
“The preventive efforts we make are important. We must understand the extent of the problem in Norway, and we must implement measures that can reduce the development of resistance. The use of integrated pest management can play an important role in this by reducing unnecessary The use of fungicides plays a role. Additionally, consideration must be given to which situations require the use of fungicides.”
The researchers concluded, “Norway is excellent at avoiding unnecessary use of antibiotics, and we should equally focus on avoiding unnecessary use of fungicides. When resistance is well established, eliminating it It is very difficult. So, we must be proactive.”
How do fungi develop resistance?
In all fungal populations, a certain genetic variation exists. This variation may make some “individuals” more tolerant of fungicides than others. When a population is exposed to fungicide, these “individuals” will survive, and can reproduce. Resistance to fungicides is genetic, and thus hereditary. Random mutations can also occur in the DNA of the fungus, causing it to become resistant. In this way, use of the same type of fungicide over a long period of time will select for fungi that are increasingly resistant. The faster the fungus can reproduce, the faster resistance can occur.
Different fungicides have different strategies for killing or preventing fungus. An “individual” who has developed resistance to one type of fungicide will not necessarily be resistant to a fungicide that works in a different way. Therefore, it is important to avoid unilateral use of fungicides with similar modes of action. Additionally, in plant production, integrated pest management (IPM) should be used to reduce the need for fungicides (and other pesticides).