An autophagosome (green) in the process of "eating" a nucleus (red) in a azole-treated cell of Z. tritici
In groundbreaking research led by the University of Exeter, scientists have found that the world’s most commonly used antifungals prompt pathogens to destroy themselves.
This discovery holds promise for enhancing methods to safeguard both food supplies and human health.
When it comes to fungal plant diseases, azole fungicides are most commonly used. Scientists have now discovered the mechanism by which azoles kill pathogenic fungi.
In a study, led by Professor Gero Steinberg investigated what happens in the case of the fungus Zymoseptoria tritici.
Azoles directly target enzymes in the pathogen cells that produce ergosterol. Ergosterol plays a crucial role in maintaining the structure and function of the fungal cell membrane, meaning that preventing its synthesis leads to cell destabilization and death.
They used live-cell imaging and molecular genetics approaches, the goal was to understand why inhibiting ergosterol synthesis results in fungal cell death.
The fungus was treated with azoles and observed the cellular response. They discovered that azoles reduce ergosterol levels, which, however, increases other metabolic processes, leading to the accumulation of toxic by-products.
This triggers a process called apoptosis, or the so-called “suicide” program. Ultimately causing the cell to consume itself, leading to macroautophagy.
Lead author Gero Steinberg stated that their findings rewrite the common understanding of how azoles kill fungal pathogens.
“We show that azoles trigger cellular ‘suicide’ programs, resulting in pathogen self-destruction. This cellular reaction occurs after two days of treatment. Suggesting that cells reach a ‘point of no return’ after a certain period of exposure to azoles,” he said.
However, this gives the pathogen additional time to develop resistance to azoles.
“Our work sheds light on the activity of our most widely used chemical control agents in crop and human pathogens worldwide,” the researcher added. The findings of the study aims to aid in refining strategies that can save lives and guarantee food security in the future.
The same mechanism was discovered in the rice fungus Magnaporthe oryzae. This fungus causes a disease that destroys about 30 percent of rice. They also tested some antifungal drugs, and all led to the same response.
In other words, they concluded that preventing ergosterol synthesis leads to the self-destruction of pathogen cells.
Fungal diseases represent a significant threat to global agriculture and human health. These diseases are responsible for the loss of up to 25% of the world’s crop production every year.
In addition to affecting plants, fungal diseases pose serious health risks to humans. They can be particularly dangerous for individuals with weakened immune systems.
One of the primary defenses against fungal diseases in agriculture is the use of azole fungicides. Azole fungicides are crucial for protecting crops from a variety of fungal pathogens, thereby helping to secure food production and maintain agricultural productivity.
The reliance on azole fungicides presents challenges. The widespread and repeated use of these chemicals can lead to the development of resistance in fungal populations.
So, there is a need for ongoing research and development of new antifungal strategies and alternative treatments to ensure effective control of fungal diseases. According to the data the world agricultural fungicide market is worth more than £3 billion per year.
The study was published in Nature Communications.
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Maria Bolevich Maria Bolevich graduated from Medical High School and Faculty of Metallurgy and Technology, Department of Environmental protection. She is an environmental protection engineer, and she wrote her first scientific article as a student in 2009 which triggered her passion for science journalism. As a science, health, and environmental journalist she has been collaborating with many international media, including Nature, SciDev… She is a recipient of a number of noteworthy awards in her field of expertise.
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