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A bacterial E3 ubiquitin ligase targets a host protein kinase to disrupt plant immunity


Many bacterial pathogens of plants and animals use a type III secretion system to deliver diverse virulence-associated ‘effector’ proteins into the host cell1. The mechanisms by which these effectors act are mostly unknown; however, they often promote disease by suppressing host immunity2. One type III effector, AvrPtoB, expressed by the plant pathogen Pseudomonas syringae pv. tomato, has a carboxy-terminal domain that is an E3 ubiquitin ligase3. Deletion of this domain allows an amino-terminal region of AvrPtoB (AvrPtoB1–387) to be detected by certain tomato varieties leading to immunity-associated programmed cell death4. Here we show that a host kinase, Fen, physically interacts with AvrPtoB1–387 and is responsible for activating the plant immune response. The AvrPtoB E3 ligase specifically ubiquitinates Fen and promotes its degradation in a proteasome-dependent manner. This degradation leads to disease susceptibility in Fen-expressing tomato lines. Various wild species of tomato were found to exhibit immunity in response to AvrPtoB1–387 and not to full-length AvrPtoB. Thus, by acquiring an E3 ligase domain, AvrPtoB has thwarted a highly conserved host resistance mechanism.

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Figure 1: The Fen kinase is responsible for the Rsb phenotype.
Figure 2: Fen is ubiquitinated in the presence of AvrPtoB.
Figure 3: In the presence of AvrPtoB, Fen is degraded in a proteasome-dependent manner.
Figure 4: Rsb is present in many cultivated and wild species of tomato.


  1. Mudgett, M. B. New insights to the function of phytopathogenic bacterial type III effectors in plants. Annu. Rev. Plant Biol. 56, 509–531 (2005)

    CAS  Article  Google Scholar 

  2. Abramovitch, R. B., Anderson, J. C. & Martin, G. B. Bacterial elicitation and evasion of plant innate immunity. Nature Rev. Mol. Cell Biol. 7, 601–611 (2006)

    CAS  Article  Google Scholar 

  3. Janjusevic, R., Abramovitch, R. B., Martin, G. B. & Stebbins, C. E. A bacterial inhibitor of host programmed cell death defenses is an E3 ubiquitin ligase. Science 311, 222–226 (2006)

    ADS  CAS  Article  Google Scholar 

  4. Abramovitch, R. B., Kim, Y.-J., Chen, S., Dickman, M. B. & Martin, G. B. Pseudomonas type III effector AvrPtoB induces plant disease susceptibility by inhibition of host programmed cell death. EMBO J. 22, 60–69 (2003)

    CAS  Article  Google Scholar 

  5. Buell, C. R. et al. The complete genome sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv. tomato DC3000. Proc. Natl Acad. Sci. USA 100, 10181–10186 (2003)

    ADS  CAS  Article  Google Scholar 

  6. Pedley, K. F. & Martin, G. B. Molecular basis of Pto-mediated resistance to bacterial speck disease. Annu. Rev. Phytopathol. 41, 215–243 (2003)

    CAS  Article  Google Scholar 

  7. Martin, G. B. et al. Map-based cloning of a protein kinase gene conferring disease resistance in tomato. Science 262, 1432–1436 (1993)

    ADS  CAS  Article  Google Scholar 

  8. Mucyn, T. S. et al. The tomato NBARC-LRR protein Prf interacts with Pto kinase in vivo to regulate specific plant immunity. Plant Cell 18, 2792–2806 (2006)

    CAS  Article  Google Scholar 

  9. Martin, G. B. et al. A member of the Pto gene family confers sensitivity to fenthion resulting in rapid cell death. Plant Cell 6, 1543–1552 (1994)

    CAS  Article  Google Scholar 

  10. Kim, Y.-J., Lin, N.-C. & Martin, G. B. Two distinct Pseudomonas effector proteins interact with the Pto kinase and activate plant immunity. Cell 109, 589–598 (2002)

    CAS  Article  Google Scholar 

  11. Abramovitch, R. B., Janjusevic, R., Stebbins, C. E. & Martin, G. B. Type III effector AvrPtoB requires intrinsic E3 ubiquitin ligase activity to suppress plant cell death and immunity. Proc. Natl Acad. Sci. USA 103, 2851–2856 (2006)

    ADS  CAS  Article  Google Scholar 

  12. Chang, J. H. et al. Functional analysis of the Pto resistance gene family in tomato and the identification of a minor resistance determinant in a susceptible haplotype. Mol. Plant Microbe Interact. 15, 281–291 (2002)

    CAS  Article  Google Scholar 

  13. Pascuzzi, P. E. Structure-based functional analyses of Pseudomonas type III effector protein AvrPto and evaluation of putative virulence targets in tomato. PhD thesis, Cornell Univ. (2006)

  14. del Pozo, O., Pedley, K. F. & Martin, G. B. MAPKKKα is a positive regulator of cell death associated with both plant immunity and disease. EMBO J. 23, 3072–3082 (2004)

    CAS  Article  Google Scholar 

  15. Jia, Y., Loh, Y.-T., Zhou, J. & Martin, G. B. Alleles of Pto and Fen occur in bacterial speck-susceptible and fenthion-insensitive tomato and encode active protein kinases. Plant Cell 9, 61–73 (1997)

    CAS  Article  Google Scholar 

  16. Riely, B. K. & Martin, G. B. Ancient origin of pathogen recognition specificity conferred by the tomato disease resistance gene Pto. Proc. Natl Acad. Sci. USA 98, 2059–2064 (2001)

    ADS  CAS  Article  Google Scholar 

  17. He, P. et al. Specific bacterial suppressors of MAMP signaling upstream of MAPKKK in Arabidopsis innate immunity. Cell 125, 563–575 (2006)

    CAS  Article  Google Scholar 

  18. de Torres, M. et al. Pseudomonas syringae effector AvrPtoB suppresses basal defence in Arabidopsis. Plant J. 47, 368–382 (2006)

    CAS  Article  Google Scholar 

  19. Badel, J. L., Shimizu, R., Oh, H. S. & Collmer, A. A Pseudomonas syringae pv. tomato avrE1/hopM1 mutant is severely reduced in growth and lesion formation in tomato. Mol. Plant Microbe Interact. 19, 99–111 (2006)

    CAS  Article  Google Scholar 

  20. Kim, M. G. et al. Two Pseudomonas syringae type III effectors inhibit RIN4-regulated basal defense in Arabidopsis. Cell 121, 749–759 (2005)

    CAS  Article  Google Scholar 

  21. Stebbins, C. E. & Galan, J. E. Structural mimicry in bacterial virulence. Nature 412, 701–705 (2001)

    ADS  CAS  Article  Google Scholar 

  22. Angot, A., Vergunst, A., Genin, S. & Peeters, N. Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems. PLoS Pathogens 3, e3 (2007)

    Article  Google Scholar 

  23. Rytkonen, A. & Holden, D. W. Bacterial interference of ubiquitination and deubiquitination. Cell Host Microbe 1, 13–22 (2007)

    CAS  Article  Google Scholar 

  24. Rohde, J. R., Breitkreutz, A., Chenal, A., Sansonetti, P. J. & Parsot, C. Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe 1, 77–83 (2007)

    CAS  Article  Google Scholar 

  25. Jamir, Y. et al. Identification of Pseudomonas syringae type III effectors that can suppress programmed cell death in plants and yeast. Plant J. 37, 554–565 (2004)

    CAS  Article  Google Scholar 

  26. Kim, H. S. et al. The Pseudomonas syringae effector AvrRpt2 cleaves its C-terminally acylated target, RIN4, from Arabidopsis membranes to block RPM1 activation. Proc. Natl Acad. Sci. USA 102, 6496–6501 (2005)

    ADS  CAS  Article  Google Scholar 

  27. Guttman, D. S. et al. A functional screen for the type III (Hrp) secretome of the plant pathogen Pseudomonas syringae. Science 295, 1722–1726 (2002)

    ADS  CAS  Article  Google Scholar 

  28. Lin, N. C., Abramovitch, R. B., Kim, Y. J. & Martin, G. B. Diverse AvrPtoB homologs from several Pseudomonas syringae pathovars elicit Pto-dependent resistance and have similar virulence activities. Appl. Environ. Microbiol. 72, 702–712 (2006)

    CAS  Article  Google Scholar 

  29. Anderson, J. C., Pascuzzi, P. E., Xiao, F., Sessa, G. & Martin, G. B. Host-mediated phosphorylation of type III effector AvrPto promotes Pseudomonas virulence and avirulence in tomato. Plant Cell 18, 502–514 (2006)

    CAS  Article  Google Scholar 

  30. Xing, T., Malik, K., Martin, T. & Miki, B. L. Activation of tomato PR and wound-related genes by a mutagenized tomato MAP kinase kinase through divergent pathways. Plant Mol. Biol. 46, 109–120 (2001)

    CAS  Article  Google Scholar 

  31. Leng, R. P. et al. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 112, 779–791 (2003)

    CAS  Article  Google Scholar 

  32. Zeng, L. R. et al. Spotted leaf11, a negative regulator of plant cell death and defense, encodes a U-box/armadillo repeat protein endowed with E3 ubiquitin ligase activity. Plant Cell 16, 2795–2808 (2004)

    CAS  Article  Google Scholar 

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We thank K. Munkvold and X. Tang for critical review of the manuscript; B. Randall for assistance with plant inoculations; J. Cohn and P. Pascuzzi for generation and characterization of the RG-PtoR(hpPto) line; J. Li and X. Tang for unpublished data; S. Collier for technical assistance; and our greenhouse staff for plant care. This work was supported, in part, by the NIH, the NSF and the Triad Foundation (G.B.M.).

Author Contributions T.R.R. and G.B.M. conceived, designed, and analysed the experiments. T.R.R. performed all of the experiments with the exceptions noted below. L.Z. performed the experiment shown in Figure 2b and Supplementary Fig. 5b. J.J.B. performed the experiments shown in Figure 1c and Supplementary Fig. 2. R.B.A. and F.X. provided technical assistance and unpublished clones. T.R.R. and G.B.M. wrote the manuscript. All authors contributed comments that were incorporated into the final version.

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Correspondence to Gregory B. Martin.

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Rosebrock, T., Zeng, L., Brady, J. et al. A bacterial E3 ubiquitin ligase targets a host protein kinase to disrupt plant immunity. Nature 448, 370–374 (2007).

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