Fungicide#Fungicide resistance management

Some major fungal threats to agriculture (and the associated diseases) are Ascomycetes ("potato late blight"), basidiomycetes ("powdery mildew"), deuteromycetes (various rusts), and oomycetes ("downy mildew").

{{Further|List of fungicides}}

Like other pesticides, fungicides are numerous and diverse. This complexity has led to diverse schemes for classifying fungicides. Classifications are based on inorganic (elemental sulfur and copper salts) vs organic, chemical structures (dithiocarbamates vs phthalimides), and, most successfully, mechanism of action (MOA). These respective classifications reflect the evolution of the underlying science.

:image:Captan Structural Formula V.1.svg, a phthalimide, is a major commercial fungicide.]]

Traditional fungicides are simple inorganic compounds like sulfur,C.Michael Hogan. 2011. [http://www.eoearth.org/article/Sulfur?topic=49557 Sulfur. Encyclopedia of Earth, eds. A.Jorgensen and C.J.Cleveland, National Council for Science and the environment, Washington DC] {{webarchive |url=https://web.archive.org/web/20121028080550/http://www.eoearth.org/article/Sulfur?topic=49557 |date=October 28, 2012 }} and copper salts. While cheap, they must be applied repeatedly and are relatively ineffective. Other active ingredients in fungicides include neem oil, rosemary oil, jojoba oil, the bacterium Bacillus subtilis, and the beneficial fungus Ulocladium oudemansii.

In the 1930s dithiocarbamate-based fungicides, the first organic compounds used for this purpose, became available. These include ferbam, ziram, zineb, maneb, and mancozeb. These compounds are non-specific and are thought to inhibit cysteine-based protease enzymes. Similarly nonspecific are N-substituted phthalimides. Members include captafol, captan, and folpet. Chlorothalonil is also non-specific.

Specific fungicides target a particular biological process in the fungus.

• bupirimate
• metalaxyl

• carbendazim
• pencycuron

Some fungicides target succinate dehydrogenase, a metabolically central enzyme. Fungi of the class Basidiomycetes were the initial focus of these fungicides. These fungi are active against cereals.

• azoxystrobin
• binapacryl
• boscalid
• carboxin
• cyazofamid
• pydiflumetofen

• blasticidin-S
• kasugamycin
• pyrimethanil

• fludioxonil
• procymidone

• propamocarb
• pyrazophos
• tecnazene

• tricyclazole

• fenpropimorph
• hexaconazole
• imazalil
• myclobutanil
• propiconazole

• dimethomorph
• polyoxins

• acibenzolar
• fosetyl-Al
• phosphorous acid{{cite journal |last1=Thao |first1=Hoang Thi Bich |last2=Yamakawa |first2=Takeo |title=Phosphite (phosphorous acid): Fungicide, fertilizer or bio-stimulator? |journal=Soil Science and Plant Nutrition |date=April 2009 |volume=55 |issue=2 |pages=228–234 |doi=10.1111/j.1747-0765.2009.00365.x|bibcode=2009SSPN...55..228T |doi-access=free }}

Some of the most common fungal crop pathogens are known to suffer from mycoviruses, and it is likely that they are as common as for plant and animal viruses, although not as well studied. Given the obligately parasitic nature of mycoviruses, it is likely that all of these are detrimental to their hosts, and thus are potential biocontrols/biofungicides.

{{See also|Antimicrobial resistance}}

Doses that provide the most control of the disease also provide the largest selection pressure to acquire resistance.{{cite journal |last1=Metcalfe |first1=R.J. |first2=M.W. |last2=Shaw |first3=P.E. |last3=Russell |date=2000 |title=The effect of dose and mobility on the strength of selection for DMI (sterol demethylation inhibitors) fungicide resistance in inoculated field experiments |journal=Plant Pathology |volume=49 |pages=546–557|doi=10.1046/j.1365-3059.2000.00486.x }}

In some cases, the pathogen evolves resistance to multiple fungicides, a phenomenon known as cross resistance. These additional fungicides typically belong to the same chemical family, act in the same way, or have a similar mechanism for detoxification. Sometimes negative cross-resistance occurs, where resistance to one chemical class of fungicides increases sensitivity to a different chemical class of fungicides. This has been seen with carbendazim and diethofencarb. Also possible is resistance to two chemically different fungicides by separate mutation events. For example, Botrytis cinerea is resistant to both azoles and dicarboximide fungicides.

A common mechanism for acquiring resistance is alteration of the target enzyme. For example, Black Sigatoka, an economically important pathogen of banana, is resistant to the QoI fungicides, due to a single nucleotide change resulting in the replacement of one amino acid (glycine) by another (alanine) in the target protein of the QoI fungicides, cytochrome b.{{cite journal |first=Helge |last=Sierotzki |title=Mode of resistance to respiration inhibitors at the cytochrome bc1 enzyme complex of Mycosphaerella fijiensis field isolates |journal=Pest Management Science |volume=56 |issue= 10|pages=833–841 |date=2000 |doi=10.1002/1526-4998(200010)56:10<833::AID-PS200>3.0.CO;2-Q }} It is presumed that this 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.{{cite journal |vauthors=Schnabel G, Jones AL |title=The 14alpha-Demethylasse(CYP51A1) Gene is Overexpressed in Venturia inaequalis Strains Resistant to Myclobutanil |journal=Phytopathology |volume=91 |issue=1 |pages=102–110 |date=January 2001 |pmid=18944284 |doi=10.1094/PHYTO.2001.91.1.102 |doi-access=free }}

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 five ABC-type transporters with overlapping substrate specificities that together work to pump toxic chemicals out of the cell.{{cite journal |vauthors=Zwiers LH, Stergiopoulos I, Gielkens MM, Goodall SD, De Waard MA |title=ABC transporters of the wheat pathogen Mycosphaerella graminicola function as protectants against biotic and xenobiotic toxic compounds |journal=Mol Genet Genomics |volume=269 |issue=4 |pages=499–507 |date=July 2003 |pmid=12768412 |doi=10.1007/s00438-003-0855-x }}

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

Fungicides that are at risk of losing their potency due to resistance include Strobilurins such as azoxystrobin.{{cite web |url=https://www.frac.info/ |title=Fungicides Resistance Action Committee website}}

Cross-resistance can occur because the active ingredients share a common mode of action. The industry-sponsored Fungicide Resistance Action Committee (FRAC), whose parent organization is CropLife International,{{cite web |title=CropLife |website=CropLife International |url=https://croplife.org/ |access-date=2025-05-02}} advises on the use of fungicides in crop protection and classifies the available compounds according to their chemical structures and mechanism of action so as to manage the risks of resistance developing.{{cite web |url=https://www.frac.info/media/kufnaceb/frac-code-list-2024.pdf |title=FRAC Code List 2024 |publisher=Fungicides Resistance Action Committee |access-date=2025-05-02}} The 2024 FRAC poster of fungicides includes all the chemicals mentioned in this article.{{cite web |url=https://www.frac.info/media/42keb12k/frac-moa-poster-2024.pdf |date=2024 |access-date=2025-05-01 |publisher=CropLife International |title=FRAC Classification of Fungicides }}

Fungicides pose risks for humans.{{cite journal |vauthors=Lini RS, Scanferla DT, de Oliveira NG, Aguera RG, Santos TD, Teixeira JJ, Kaneshima AM, Mossini SA |title=Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review |journal=Crit Rev Toxicol |volume=54 |issue=1 |pages=35–54 |date=January 2024 |pmid=38288970 |doi=10.1080/10408444.2024.2303481 }}

Fungicide residues have been found on food for human consumption, mostly from post-harvest treatments.{{cite book |title=Pesticide Chemistry and Bioscience |editor-first=G.T |editor-last=Brooks and |editor2-first=T.R |editor2-last=Roberts |date=1999 |publisher=Royal Society of Chemistry |doi=10.1533/9781845698416 |isbn=978-1-84569-841-6 |oclc=849886156}} Some fungicides are dangerous to human health, such as vinclozolin, which has now been removed from use.{{cite journal |vauthors=Hrelia P, Fimognari C, Maffei F, Vigagni F, Mesirca R, Pozzetti L, Paolini M, Cantelli Forti G |title=The genetic and non-genetic toxicity of the fungicide Vinclozolin |journal=Mutagenesis |volume=11 |issue=5 |pages=445–53 |date=September 1996 |pmid=8921505 |doi=10.1093/mutage/11.5.445 }} Ziram is also a fungicide that is toxic to humans with long-term exposure, and fatal if ingested.National Center for Biotechnology Information. PubChem Compound Database; CID=8722, https://pubchem.ncbi.nlm.nih.gov/compound/8722 (accessed Jan. 13, 2019) A number of fungicides are also used in human health care.

• Antifungal drug
• Index of pesticide articles
• PHI-base (Pathogen-Host-Interaction database)
• Phytopathology
• Plant disease forecasting

==Further reading==

• {{cite journal | url=https://doi.org/10.1007%2FBF02015493 | doi=10.1007/BF02015493 | title=Interaction of 2,4,5-trichlorophenylsulphonylmethyl thiocyanate with fungal spores | year=1969 | last1=Haverkate | first1=F. | last2=Tempel | first2=A. | last3=Held | first3=A. J. | journal=Netherlands Journal of Plant Pathology | volume=75 | issue=5 | pages=308–315 | bibcode=1969EJPP...75..308H | s2cid=23304303 }}

{{Reflist|30em|refs=

{{cite journal | last1=Pearson | first1=M.N. | last2=Beever | first2=R.E. | last3=Boine | first3=B. | last4=Arthur | first4=K. | title=Mycoviruses of filamentous fungi and their relevance to plant pathology |type=Review | journal=Molecular Plant Pathology | volume=10 | issue=1 | year=2009 | doi=10.1111/j.1364-3703.2008.00503.x | pages=115–128 | s2cid=34331588| pmid=19161358 | pmc=6640375}}

}}

• [http://www.frac.info Fungicide Resistance Action Committee]
• [https://web.archive.org/web/20071223002409/http://frag.csl.gov.uk/cropspecific.cfm Fungicide Resistance Action Group], United Kingdom
• [http://npic.orst.edu/gen.htm General Pesticide Information] {{Webarchive|url=https://web.archive.org/web/20071229105917/http://npic.orst.edu/gen.htm |date=2007-12-29 }} - National Pesticide Information Center, Oregon State University, United States

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Category:Mycology

Category:Biocides