Fungicide - Resistance

Resistance

Pathogens respond to the use of fungicides by evolving resistance. In the field several mechanisms of resistance have been identified. The evolution of fungicide resistance can be gradual or sudden. In qualitative or discrete resistance a mutation (normally to a single gene) produces a race of a fungus with a high degree of resistance. Such resistant varieties also tend to show stability, persisting after the fungicide has been removed from the market. For example sugar beet leaf blotch remains resistant to azoles years after they were no longer used for control of the disease. This is because such mutations often have a high selection pressure when the fungicide is used, but there is low selection pressure to remove them in the absence of the fungicide.

In instances where resistance occurs more gradually a shift in sensitivity in the pathogen to the fungicide can be seen. Such resistance is polygenic – an accumulation of many mutation in different genes each having a small additive effect. This type of resistance is known as quantitative or continuous resistance. In this kind of resistance the pathogen population will revert back to a sensitive state if the fungicide is no longer applied.

Little is known about how variations in fungicide treatment affect the selection pressure to evolve resistance to that fungicide. Evidence shows that the doses that provide the most control of the disease also provide the largest selection pressure to acquire resistance, and that lower doses decreased the selection pressure.

In some cases when a pathogen evolves resistance to one fungicide it automatically obtains resistance to others – a phenomenon known as cross resistance. These additional fungicides are normally of the same chemical family or have the same mode of action, or can be detoxified by the same mechanism. Sometimes negative cross resistance occurs, where resistance to one chemical class of fungicides leads to an increase in sensitivity to a different chemical class of fungicides. This has been seen with carbendazim and diethofencarb.

There are also recorded incidences of pathogens evolving multiple drug resistance – resistance to two chemically different fungicides by separate mutation events. For example Botrytis cinerea is resistant to both azoles and dicarboximide fungicides.

There are several routes by which pathogens can evolve fungicide resistance. The most common mechanism appears to be alteration of the target site, particular as a defence against single site of action fungicides. For example Black Sigatoka, an economically important pathogen of banana, is resistant to the QoI fungicides, due to a single nucleotide change resulting one amino acid (glycine) being replaced by another (alanine) in the target protein of the QoI fungicides, cytochrome b. This presumably disrupts the binding of the fungicide to the protein, rendering the fungicide ineffective.

Upregulation of target genes can also render the fungicide ineffective. This is seen in DMI resistant strains of Venturia inaequalis.

Resistance to fungicides can also be developed by efficient efflux of the fungicide out of the cell. Septoria tritici has developed multiple drug resistance using this mechanism. The pathogen had 5 ABC type transporters with overlapping substrate specificities that together work to effectively pump toxic chemicals out of the cell.

In addition to the mechanisms outlined above, fungi may also develop metabolic pathways that circumvent the target protein, or acquire enzymes that enable metabolism of the fungicide to a harmless substance.