Phenylpyrroles: 30 Years, Two Molecules and (Nearly) No Resistance

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2016 Dec 27

PMID 28018333

Citations 32

Authors

Jaafar Kilani

Sabine Fillinger

Affiliations

Soon will be listed here.

Abstract

Phenylpyrroles are chemical analogs of the natural antifungal compound pyrrolnitrin. Fenpiclonil, but mainly fludioxonil are registered against multiple fungal crop diseases since over 25 years for seed or foliar treatment. They have severe physiological impacts on the pathogen, including membrane hyperpolarization, changes in carbon metabolism and the accumulation of metabolites leading to hyphal swelling and burst. The selection and characterization of mutants resistant to phenylpyrroles have revealed that these fungicides activate the fungal osmotic signal transduction pathway through their perception by a typical fungal hybrid histidine kinase (HHK). The HHK is prone to point mutations that confer fungicide resistance and affect its sensor domain, composed of tandem repeats of HAMP motifs. Fludioxonil resistant mutants have been selected in many fungal species under laboratory conditions. Generally they present severe impacts on fitness parameters. Since only few cases of field resistance specific to phenylpyrroles have been reported one may suspect that the fitness penalty of phenylpyrrole resistance is the reason for the lack of field resistance.

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References

Zhang Y, Lamm R, Pillonel C, Lam S, Xu J . Osmoregulation and fungicide resistance: the Neurospora crassa os-2 gene encodes a HOG1 mitogen-activated protein kinase homologue. Appl Environ Microbiol. 2002; 68(2):532-8. PMC: 126731. DOI: 10.1128/AEM.68.2.532-538.2002. View

Herivaux A, So Y, Gastebois A, Latge J, Bouchara J, Bahn Y . Major Sensing Proteins in Pathogenic Fungi: The Hybrid Histidine Kinase Family. PLoS Pathog. 2016; 12(7):e1005683. PMC: 4965123. DOI: 10.1371/journal.ppat.1005683. View

Walker A, Micoud A, Remuson F, Grosman J, Gredt M, Leroux P . French vineyards provide information that opens ways for effective resistance management of Botrytis cinerea (grey mould). Pest Manag Sci. 2013; 69(6):667-78. DOI: 10.1002/ps.3506. View

Dry I, Yuan K, Hutton D . Dicarboximide resistance in field isolates of Alternaria alternata is mediated by a mutation in a two-component histidine kinase gene. Fungal Genet Biol. 2003; 41(1):102-8. DOI: 10.1016/j.fgb.2003.09.002. View

Matamouros S, Hager K, Miller S . HAMP Domain Rotation and Tilting Movements Associated with Signal Transduction in the PhoQ Sensor Kinase. mBio. 2015; 6(3):e00616-15. PMC: 4447245. DOI: 10.1128/mBio.00616-15. View

Kretschmer M, Leroch M, Mosbach A, Walker A, Fillinger S, Mernke D . Fungicide-driven evolution and molecular basis of multidrug resistance in field populations of the grey mould fungus Botrytis cinerea. PLoS Pathog. 2009; 5(12):e1000696. PMC: 2785876. DOI: 10.1371/journal.ppat.1000696. View

Meena N, Kaur H, Mondal A . Interactions among HAMP domain repeats act as an osmosensing molecular switch in group III hybrid histidine kinases from fungi. J Biol Chem. 2010; 285(16):12121-32. PMC: 2852951. DOI: 10.1074/jbc.M109.075721. View

Segmuller N, Ellendorf U, Tudzynski B, Tudzynski P . BcSAK1, a stress-activated mitogen-activated protein kinase, is involved in vegetative differentiation and pathogenicity in Botrytis cinerea. Eukaryot Cell. 2006; 6(2):211-21. PMC: 1797955. DOI: 10.1128/EC.00153-06. View

Klose D, Voskoboynikova N, Orban-Glass I, Rickert C, Engelhard M, Klare J . Light-induced switching of HAMP domain conformation and dynamics revealed by time-resolved EPR spectroscopy. FEBS Lett. 2014; 588(21):3970-6. DOI: 10.1016/j.febslet.2014.09.012. View

10.

Rupp S, Weber R, Rieger D, Detzel P, Hahn M . Spread of Strains with Multiple Fungicide Resistance in German Horticulture. Front Microbiol. 2017; 7:2075. PMC: 5206850. DOI: 10.3389/fmicb.2016.02075. View

11.

Oshima M, Fujimura M, Banno S, Hashimoto C, Motoyama T, Ichiishi A . A Point Mutation in the Two-Component Histidine Kinase BcOS-1 Gene Confers Dicarboximide Resistance in Field Isolates of Botrytis cinerea. Phytopathology. 2008; 92(1):75-80. DOI: 10.1094/PHYTO.2002.92.1.75. View

12.

Bahn Y, Kojima K, Cox G, Heitman J . Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans. Mol Biol Cell. 2005; 16(5):2285-300. PMC: 1087235. DOI: 10.1091/mbc.e04-11-0987. View

13.

Fillinger S, Ajouz S, Nicot P, Leroux P, Bardin M . Functional and structural comparison of pyrrolnitrin- and iprodione-induced modifications in the class III histidine-kinase Bos1 of Botrytis cinerea. PLoS One. 2012; 7(8):e42520. PMC: 3418262. DOI: 10.1371/journal.pone.0042520. View

14.

Ma Q, Roy F, Herrmann S, Taylor B, Johnson M . The Aer protein of Escherichia coli forms a homodimer independent of the signaling domain and flavin adenine dinucleotide binding. J Bacteriol. 2004; 186(21):7456-9. PMC: 523205. DOI: 10.1128/JB.186.21.7456-7459.2004. View

15.

Mueller D, Hartman G, Pedersen W . Development of Sclerotia and Apothecia of Sclerotinia sclerotiorum from Infected Soybean Seed and Its Control by Fungicide Seed Treatment. Plant Dis. 2019; 83(12):1113-1115. DOI: 10.1094/PDIS.1999.83.12.1113. View

16.

Foureau E, Clastre M, Obando Montoya E, Besseau S, Oudin A, Glevarec G . Subcellular localization of the histidine kinase receptors Sln1p, Nik1p and Chk1p in the yeast CTG clade species Candida guilliermondii. Fungal Genet Biol. 2014; 65:25-36. DOI: 10.1016/j.fgb.2014.01.007. View

17.

Hagiwara D, Matsubayashi Y, Marui J, Furukawa K, Yamashino T, Kanamaru K . Characterization of the NikA histidine kinase implicated in the phosphorelay signal transduction of Aspergillus nidulans, with special reference to fungicide responses. Biosci Biotechnol Biochem. 2007; 71(3):844-7. DOI: 10.1271/bbb.70051. View

18.

Hohmann S . Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev. 2002; 66(2):300-72. PMC: 120784. DOI: 10.1128/MMBR.66.2.300-372.2002. View

19.

Schumacher M, Enderlin C, Selitrennikoff C . The osmotic-1 locus of Neurospora crassa encodes a putative histidine kinase similar to osmosensors of bacteria and yeast. Curr Microbiol. 1997; 34(6):340-7. DOI: 10.1007/s002849900193. View

20.

Lavin J, Ramirez L, Ussery D, Pisabarro A, Oguiza J . Genomic analysis of two-component signal transduction proteins in basidiomycetes. J Mol Microbiol Biotechnol. 2010; 18(2):63-73. DOI: 10.1159/000277654. View