Skip to main content
The Plant Cell logoLink to The Plant Cell
. 1998 Nov;10(11):1903–1914. doi: 10.1105/tpc.10.11.1903

Impaired fungicide activity in plants blocked in disease resistance signal transduction.

A Molina 1, M D Hunt 1, J A Ryals 1
PMCID: PMC143963  PMID: 9811797

Abstract

Fungicide action is generally assumed to be dependent on an antibiotic effect on a target pathogen, although a role for plant defense mechanisms as mediators of fungicide action has not been excluded. Here, we demonstrate that in Arabidopsis, the innate plant defense mechanism contributes to the effectiveness of fungicides. In NahG and nim1 (for noninducible immunity) Arabidopsis plants, which normally exhibit increased susceptibility to pathogens, the fungicides metalaxyl, fosetyl, and Cu(OH)2 are much less active and fail to control Peronospora parasitica. In contrast, the effectiveness of these fungicides is not altered in Arabidopsis mutants defective in the ethylene or jasmonic acid signal transduction pathways. Application of the systemic acquired resistance activator benzothiadiazole (BTH) in combination with these fungicides results in a synergistic effect on pathogen resistance in wild-type plants and an additive effect in NahG and BTH-unresponsive nim1 plants. Interestingly, BTH treatment normally induces long-lasting pathogen protection; however, in NahG plants, the protection is transient. These observations suggest that BTH treatment can compensate only partially for an impaired signal transduction pathway and support the idea that pathogen defense mechanisms are under positive feedback control. These observations are strikingly reminiscent of the reduced efficacy of antifungal agents in immunocompromised animals.

Full Text

The Full Text of this article is available as a PDF (221.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Araujo F. G., Hunter C. A., Remington J. S. Treatment with interleukin 12 in combination with atovaquone or clindamycin significantly increases survival of mice with acute toxoplasmosis. Antimicrob Agents Chemother. 1997 Jan;41(1):188–190. doi: 10.1128/aac.41.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baeuerle P. A., Baltimore D. NF-kappa B: ten years after. Cell. 1996 Oct 4;87(1):13–20. doi: 10.1016/s0092-8674(00)81318-5. [DOI] [PubMed] [Google Scholar]
  3. Baker B., Zambryski P., Staskawicz B., Dinesh-Kumar S. P. Signaling in plant-microbe interactions. Science. 1997 May 2;276(5313):726–733. doi: 10.1126/science.276.5313.726. [DOI] [PubMed] [Google Scholar]
  4. Baldwin A. S., Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683. doi: 10.1146/annurev.immunol.14.1.649. [DOI] [PubMed] [Google Scholar]
  5. Bent A. F. Plant Disease Resistance Genes: Function Meets Structure. Plant Cell. 1996 Oct;8(10):1757–1771. doi: 10.1105/tpc.8.10.1757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bergey D. R., Howe G. A., Ryan C. A. Polypeptide signaling for plant defensive genes exhibits analogies to defense signaling in animals. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12053–12058. doi: 10.1073/pnas.93.22.12053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bleecker A. B., Estelle M. A., Somerville C., Kende H. Insensitivity to Ethylene Conferred by a Dominant Mutation in Arabidopsis thaliana. Science. 1988 Aug 26;241(4869):1086–1089. doi: 10.1126/science.241.4869.1086. [DOI] [PubMed] [Google Scholar]
  8. Bonas U., Van den Ackervaken G. Recognition of bacterial avirulence proteins occurs inside the plant cell: a general phenomenon in resistance to bacterial diseases? Plant J. 1997 Jul;12(1):1–7. doi: 10.1046/j.1365-313x.1997.12010001.x. [DOI] [PubMed] [Google Scholar]
  9. Bowling S. A., Clarke J. D., Liu Y., Klessig D. F., Dong X. The cpr5 mutant of Arabidopsis expresses both NPR1-dependent and NPR1-independent resistance. Plant Cell. 1997 Sep;9(9):1573–1584. doi: 10.1105/tpc.9.9.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bowling S. A., Guo A., Cao H., Gordon A. S., Klessig D. F., Dong X. A mutation in Arabidopsis that leads to constitutive expression of systemic acquired resistance. Plant Cell. 1994 Dec;6(12):1845–1857. doi: 10.1105/tpc.6.12.1845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cao H., Bowling S. A., Gordon A. S., Dong X. Characterization of an Arabidopsis Mutant That Is Nonresponsive to Inducers of Systemic Acquired Resistance. Plant Cell. 1994 Nov;6(11):1583–1592. doi: 10.1105/tpc.6.11.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cao H., Glazebrook J., Clarke J. D., Volko S., Dong X. The Arabidopsis NPR1 gene that controls systemic acquired resistance encodes a novel protein containing ankyrin repeats. Cell. 1997 Jan 10;88(1):57–63. doi: 10.1016/s0092-8674(00)81858-9. [DOI] [PubMed] [Google Scholar]
  13. Casadevall A. Crisis in infectious diseases: time for a new paradigm? Clin Infect Dis. 1996 Oct;23(4):790–794. doi: 10.1093/clinids/23.4.790. [DOI] [PubMed] [Google Scholar]
  14. Century K. S., Holub E. B., Staskawicz B. J. NDR1, a locus of Arabidopsis thaliana that is required for disease resistance to both a bacterial and a fungal pathogen. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6597–6601. doi: 10.1073/pnas.92.14.6597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dangl J. L., Dietrich R. A., Richberg M. H. Death Don't Have No Mercy: Cell Death Programs in Plant-Microbe Interactions. Plant Cell. 1996 Oct;8(10):1793–1807. doi: 10.1105/tpc.8.10.1793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Deckert-Schlüter M., Rang A., Weiner D., Huang S., Wiestler O. D., Hof H., Schlüter D. Interferon-gamma receptor-deficiency renders mice highly susceptible to toxoplasmosis by decreased macrophage activation. Lab Invest. 1996 Dec;75(6):827–841. [PubMed] [Google Scholar]
  18. Delaney T. P., Friedrich L., Ryals J. A. Arabidopsis signal transduction mutant defective in chemically and biologically induced disease resistance. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6602–6606. doi: 10.1073/pnas.92.14.6602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Delaney T. P. Genetic dissection of acquired resistance to disease. Plant Physiol. 1997 Jan;113(1):5–12. doi: 10.1104/pp.113.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Delaney T. P., Uknes S., Vernooij B., Friedrich L., Weymann K., Negrotto D., Gaffney T., Gut-Rella M., Kessmann H., Ward E., Ryals J. A central role of salicylic Acid in plant disease resistance. Science. 1994 Nov 18;266(5188):1247–1250. doi: 10.1126/science.266.5188.1247. [DOI] [PubMed] [Google Scholar]
  21. Dietrich R. A., Delaney T. P., Uknes S. J., Ward E. R., Ryals J. A., Dangl J. L. Arabidopsis mutants simulating disease resistance response. Cell. 1994 May 20;77(4):565–577. doi: 10.1016/0092-8674(94)90218-6. [DOI] [PubMed] [Google Scholar]
  22. Ecker J. R., Davis R. W. Plant defense genes are regulated by ethylene. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5202–5206. doi: 10.1073/pnas.84.15.5202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gaffney T., Friedrich L., Vernooij B., Negrotto D., Nye G., Uknes S., Ward E., Kessmann H., Ryals J. Requirement of salicylic Acid for the induction of systemic acquired resistance. Science. 1993 Aug 6;261(5122):754–756. doi: 10.1126/science.261.5122.754. [DOI] [PubMed] [Google Scholar]
  24. Georgopapadakou N. H., Walsh T. J. Antifungal agents: chemotherapeutic targets and immunologic strategies. Antimicrob Agents Chemother. 1996 Feb;40(2):279–291. doi: 10.1128/aac.40.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Glazebrook J., Rogers E. E., Ausubel F. M. Isolation of Arabidopsis mutants with enhanced disease susceptibility by direct screening. Genetics. 1996 Jun;143(2):973–982. doi: 10.1093/genetics/143.2.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Greenberg J. T., Guo A., Klessig D. F., Ausubel F. M. Programmed cell death in plants: a pathogen-triggered response activated coordinately with multiple defense functions. Cell. 1994 May 20;77(4):551–563. doi: 10.1016/0092-8674(94)90217-8. [DOI] [PubMed] [Google Scholar]
  27. Guzmán P., Ecker J. R. Exploiting the triple response of Arabidopsis to identify ethylene-related mutants. Plant Cell. 1990 Jun;2(6):513–523. doi: 10.1105/tpc.2.6.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Görlach J., Volrath S., Knauf-Beiter G., Hengy G., Beckhove U., Kogel K. H., Oostendorp M., Staub T., Ward E., Kessmann H. Benzothiadiazole, a novel class of inducers of systemic acquired resistance, activates gene expression and disease resistance in wheat. Plant Cell. 1996 Apr;8(4):629–643. doi: 10.1105/tpc.8.4.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hammond-Kosack K. E., Jones J. D. Resistance gene-dependent plant defense responses. Plant Cell. 1996 Oct;8(10):1773–1791. doi: 10.1105/tpc.8.10.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Israelski D., Remington J. Activity of gamma interferon in combination with pyrimethamine or clindamycin in treatment of murine toxoplasmosis. Eur J Clin Microbiol Infect Dis. 1990 May;9(5):358–360. doi: 10.1007/BF01973746. [DOI] [PubMed] [Google Scholar]
  31. Kogel K. H., Beckhove U., Dreschers J., Munch S., Romme Y. Acquired Resistance in Barley (The Resistance Mechanism Induced by 2,6-Dichloroisonicotinic Acid Is a Phenocopy of a Genetically Based Mechanism Governing Race-Specific Powdery Mildew Resistance). Plant Physiol. 1994 Dec;106(4):1269–1277. doi: 10.1104/pp.106.4.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lagrimini L. M., Burkhart W., Moyer M., Rothstein S. Molecular cloning of complementary DNA encoding the lignin-forming peroxidase from tobacco: Molecular analysis and tissue-specific expression. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7542–7546. doi: 10.1073/pnas.84.21.7542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lawton K. A., Friedrich L., Hunt M., Weymann K., Delaney T., Kessmann H., Staub T., Ryals J. Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway. Plant J. 1996 Jul;10(1):71–82. doi: 10.1046/j.1365-313x.1996.10010071.x. [DOI] [PubMed] [Google Scholar]
  34. Lawton K. A., Potter S. L., Uknes S., Ryals J. Acquired Resistance Signal Transduction in Arabidopsis Is Ethylene Independent. Plant Cell. 1994 May;6(5):581–588. doi: 10.1105/tpc.6.5.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lawton K., Weymann K., Friedrich L., Vernooij B., Uknes S., Ryals J. Systemic acquired resistance in Arabidopsis requires salicylic acid but not ethylene. Mol Plant Microbe Interact. 1995 Nov-Dec;8(6):863–870. doi: 10.1094/mpmi-8-0863. [DOI] [PubMed] [Google Scholar]
  36. Lemaitre B., Nicolas E., Michaut L., Reichhart J. M., Hoffmann J. A. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996 Sep 20;86(6):973–983. doi: 10.1016/s0092-8674(00)80172-5. [DOI] [PubMed] [Google Scholar]
  37. Maher E. A., Bate N. J., Ni W., Elkind Y., Dixon R. A., Lamb C. J. Increased disease susceptibility of transgenic tobacco plants with suppressed levels of preformed phenylpropanoid products. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7802–7806. doi: 10.1073/pnas.91.16.7802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Malamy J., Carr J. P., Klessig D. F., Raskin I. Salicylic Acid: a likely endogenous signal in the resistance response of tobacco to viral infection. Science. 1990 Nov 16;250(4983):1002–1004. doi: 10.1126/science.250.4983.1002. [DOI] [PubMed] [Google Scholar]
  39. Mauch-Mani B., Slusarenko A. J. Production of Salicylic Acid Precursors Is a Major Function of Phenylalanine Ammonia-Lyase in the Resistance of Arabidopsis to Peronospora parasitica. Plant Cell. 1996 Feb;8(2):203–212. doi: 10.1105/tpc.8.2.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Métraux J. P., Signer H., Ryals J., Ward E., Wyss-Benz M., Gaudin J., Raschdorf K., Schmid E., Blum W., Inverardi B. Increase in salicylic Acid at the onset of systemic acquired resistance in cucumber. Science. 1990 Nov 16;250(4983):1004–1006. doi: 10.1126/science.250.4983.1004. [DOI] [PubMed] [Google Scholar]
  41. Parker J. E., Coleman M. J., Szabò V., Frost L. N., Schmidt R., van der Biezen E. A., Moores T., Dean C., Daniels M. J., Jones J. D. The Arabidopsis downy mildew resistance gene RPP5 shares similarity to the toll and interleukin-1 receptors with N and L6. Plant Cell. 1997 Jun;9(6):879–894. doi: 10.1105/tpc.9.6.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rasmussen J. B., Hammerschmidt R., Zook M. N. Systemic Induction of Salicylic Acid Accumulation in Cucumber after Inoculation with Pseudomonas syringae pv syringae. Plant Physiol. 1991 Dec;97(4):1342–1347. doi: 10.1104/pp.97.4.1342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Roilides E., Holmes A., Blake C., Pizzo P. A., Walsh T. J. Effects of granulocyte colony-stimulating factor and interferon-gamma on antifungal activity of human polymorphonuclear neutrophils against pseudohyphae of different medically important Candida species. J Leukoc Biol. 1995 Apr;57(4):651–656. doi: 10.1002/jlb.57.4.651. [DOI] [PubMed] [Google Scholar]
  44. Roilides E., Lyman C. A., Mertins S. D., Cole D. J., Venzon D., Pizzo P. A., Chanock S. J., Walsh T. J. Ex vivo effects of macrophage colony-stimulating factor on human monocyte activity against fungal and bacterial pathogens. Cytokine. 1996 Jan;8(1):42–48. doi: 10.1006/cyto.1996.0006. [DOI] [PubMed] [Google Scholar]
  45. Ryals J. A., Neuenschwander U. H., Willits M. G., Molina A., Steiner H. Y., Hunt M. D. Systemic Acquired Resistance. Plant Cell. 1996 Oct;8(10):1809–1819. doi: 10.1105/tpc.8.10.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Ryals J., Weymann K., Lawton K., Friedrich L., Ellis D., Steiner H. Y., Johnson J., Delaney T. P., Jesse T., Vos P. The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor I kappa B. Plant Cell. 1997 Mar;9(3):425–439. doi: 10.1105/tpc.9.3.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Ryan C. A. The search for the proteinase inhibitor-inducing factor, PIIF. Plant Mol Biol. 1992 May;19(1):123–133. doi: 10.1007/BF00015610. [DOI] [PubMed] [Google Scholar]
  48. Shah J., Tsui F., Klessig D. F. Characterization of a salicylic acid-insensitive mutant (sai1) of Arabidopsis thaliana, identified in a selective screen utilizing the SA-inducible expression of the tms2 gene. Mol Plant Microbe Interact. 1997 Jan;10(1):69–78. doi: 10.1094/MPMI.1997.10.1.69. [DOI] [PubMed] [Google Scholar]
  49. Shirasu K., Nakajima H., Rajasekhar V. K., Dixon R. A., Lamb C. Salicylic acid potentiates an agonist-dependent gain control that amplifies pathogen signals in the activation of defense mechanisms. Plant Cell. 1997 Feb;9(2):261–270. doi: 10.1105/tpc.9.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Staswick P. E., Su W., Howell S. H. Methyl jasmonate inhibition of root growth and induction of a leaf protein are decreased in an Arabidopsis thaliana mutant. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6837–6840. doi: 10.1073/pnas.89.15.6837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Suzuki Y., Orellana M. A., Schreiber R. D., Remington J. S. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. 1988 Apr 22;240(4851):516–518. doi: 10.1126/science.3128869. [DOI] [PubMed] [Google Scholar]
  52. Thulke O., Conrath U. Salicylic acid has a dual role in the activation of defence-related genes in parsley. Plant J. 1998 Apr;14(1):35–42. doi: 10.1046/j.1365-313X.1998.00093.x. [DOI] [PubMed] [Google Scholar]
  53. Uknes S., Mauch-Mani B., Moyer M., Potter S., Williams S., Dincher S., Chandler D., Slusarenko A., Ward E., Ryals J. Acquired resistance in Arabidopsis. Plant Cell. 1992 Jun;4(6):645–656. doi: 10.1105/tpc.4.6.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Urban J. F., Jr, Fayer R., Chen S. J., Gause W. C., Gately M. K., Finkelman F. D. IL-12 protects immunocompetent and immunodeficient neonatal mice against infection with Cryptosporidium parvum. J Immunol. 1996 Jan 1;156(1):263–268. [PubMed] [Google Scholar]
  55. Ward E. R., Uknes S. J., Williams S. C., Dincher S. S., Wiederhold D. L., Alexander D. C., Ahl-Goy P., Metraux J. P., Ryals J. A. Coordinate Gene Activity in Response to Agents That Induce Systemic Acquired Resistance. Plant Cell. 1991 Oct;3(10):1085–1094. doi: 10.1105/tpc.3.10.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Weymann K., Hunt M., Uknes S., Neuenschwander U., Lawton K., Steiner H. Y., Ryals J. Suppression and Restoration of Lesion Formation in Arabidopsis lsd Mutants. Plant Cell. 1995 Dec;7(12):2013–2022. doi: 10.1105/tpc.7.12.2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. de Martin R., Vanhove B., Cheng Q., Hofer E., Csizmadia V., Winkler H., Bach F. H. Cytokine-inducible expression in endothelial cells of an I kappa B alpha-like gene is regulated by NF kappa B. EMBO J. 1993 Jul;12(7):2773–2779. doi: 10.1002/j.1460-2075.1993.tb05938.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Plant Cell are provided here courtesy of Oxford University Press

RESOURCES