Cited by 89Plant Pathogenic Bacteria StudiesPlant-Microbe Interactions and ImmunityAutophagy in Disease and Therapy

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A bacterial effector counteracts host autophagy by promoting degradation of an autophagy component

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Abstract

Beyond its role in cellular homeostasis, autophagy plays anti- and promicrobial roles in host-microbe interactions, both in animals and plants. One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy. Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination. Although well-described in animals, the extent to which xenophagy contributes to plant-bacteria interactions remains unknown. Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type-III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection. Intriguingly, XopL is targeted for degradation by defense-related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery. Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense-related autophagy in plant-bacteria interactions.

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Crossref · 10.15252/embj.2021110352

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Research works printed but not linked: 68

  1. Adams EHG, Spoel SH (2018) The ubiquitin‐proteasome system as a transcriptional regulator of plant immunity. J Exp Bot 69: 4529–4537 · DOI
  2. Adlung N, Prochaska H, Thieme S, Banik A, Blüher D, John P, Nagel O, Schulze S, Gantner J, Delker C et al (2016) Non‐host resistance induced by the Xanthomonas Effector XopQ is widespread within the genus nicotiana and functionally depends on EDS1. Front Plant Sci 7: 1796 · DOI
  3. Ahn G, Kim H, Kim DH, Hanh H, Yoon Y, Singaram I, Wijesinghe KJ, Johnson KA, Zhuang X, Liang Z et al (2017) SH3 Domain‐containing protein 2 plays a crucial role at the step of membrane tubulation during cell plate formation. Plant Cell 29: 1388–1405 · DOI
  4. Albers P, Üstün S, Witzel K, Kraner M, Börnke F (2019) A remorin from Nicotiana benthamiana interacts with the Pseudomonas type‐III effector protein HopZ1a and is phosphorylated by the immune‐related kinase PBS1. Mol Plant Microbe Interact 32: 1229–1242 · DOI
  5. Banfield MJ (2015) Perturbation of host ubiquitin systems by plant pathogen/pest effector proteins. Cell Microbiol 17: 18–25 · DOI
  6. Borchert N, Dieterich C, Krug K, Schutz W, Jung S, Nordheim A, Sommer RJ, Macek B (2010) Proteogenomics of Pristionchus pacificus reveals distinct proteome structure of nematode models. Genome Res 20: 837–846 · DOI
  7. Büttner D (2016) Behind the lines‐actions of bacterial type III effector proteins in plant cells. FEMS Microbiol Rev 40: 894–937 · DOI
  8. Chai Q, Wang X, Qiang L, Zhang Y, Ge P, Lu Z, Zhong Y, Li B, Wang J, Zhang L et al (2019) A Mycobacterium tuberculosis surface protein recruits ubiquitin to trigger host xenophagy. Nat Commun 10: 1973 · DOI
  9. Clough SJ, Bent AF (1998) Floral dip: a simplified method for Agrobacterium‐mediated transformation of Arabidopsis thaliana. Plant J 16: 735–743 · DOI
  10. Dagdas YF, Belhaj K, Maqbool A, Chaparro‐Garcia A, Pandey P, Petre B, Tabassum N, Cruz‐Mireles N, Hughes RK, Sklenar J et al (2016) An effector of the Irish potato famine pathogen antagonizes a host autophagy cargo receptor. Elife 5: e10856 · DOI
  11. Dagdas YF, Pandey P, Tumtas Y, Sanguankiattichai N, Belhaj K, Duggan C, Leary AY, Segretin ME, Contreras MP, Savage Z et al (2018) Host autophagy machinery is diverted to the pathogen interface to mediate focal defense responses against the Irish potato famine pathogen. Elife 7: e37476 · DOI
  12. Dauphinee AN, Cardoso C, Dalman K, Ohlsson JA, Fick SB, Robert S, Hicks GR, Bozhkov PV, Minina EA (2019) Chemical screening pipeline for identification of specific plant autophagy modulators. Plant Physiol 181: 855–866 · DOI · Paper page
  13. Dupont N, Lacas‐Gervais S, Bertout J, Paz I, Freche B, Van Nhieu GT, van der Goot FG, Sansonetti PJ, Lafont F (2009) Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy. Cell Host Microbe 6: 137–149 · DOI
  14. Erickson JL, Adlung N, Lampe C, Bonas U, Schattat MH (2018) The Xanthomonas effector XopL uncovers the role of microtubules in stromule extension and dynamics in Nicotiana benthamiana. Plant J 93: 856–870 · DOI
  15. Furlan G, Klinkenberg J, Trujillo M (2012) Regulation of plant immune receptors by ubiquitination. Front Plant Sci 3: 238 · DOI
  16. Furlan G, Nakagami H, Eschen‐Lippold L, Jiang X, Majovsky P, Kowarschik K, Hoehenwarter W, Lee J, Trujillo M (2017) Changes in PUB22 ubiquitination modes triggered by MITOGEN‐ACTIVATED PROTEIN KINASE3 dampen the immune response. Plant Cell 29: 726–745 · DOI
  17. Gantner J, Ordon J, Kretschmer C, Guerois R, Stuttmann J (2019) An EDS1‐SAG101 complex is essential for TNL‐mediated immunity in Nicotiana benthamiana. Plant Cell 31: 2456–2474 · DOI
  18. Germic N, Frangez Z, Yousefi S, Simon HU (2019) Regulation of the innate immune system by autophagy: neutrophils, eosinophils, mast cells, NK cells. Cell Death Differ 26: 703–714 · DOI
  19. Grefen C, Donald N, Hashimoto K, Kudla J, Schumacher K, Blatt MR (2010) A ubiquitin‐10 promoter‐based vector set for fluorescent protein tagging facilitates temporal stability and native protein distribution in transient and stable expression studies. Plant J 64: 355–365 · DOI
  20. Gu Y, Zavaliev R, Dong X (2017) Membrane trafficking in plant immunity. Mol Plant 10: 1026–1034 · DOI
  21. Hafrén A, Macia JL, Love AJ, Milner JJ, Drucker M, Hofius D (2017) Selective autophagy limits cauliflower mosaic virus infection by NBR1‐mediated targeting of viral capsid protein and particles. Proc Natl Acad Sci USA 114: E2026–E2035 · DOI
  22. Hafrén A, Üstün S, Hochmuth A, Svenning S, Johansen T, Hofius D (2018) Turnip mosaic virus counteracts selective autophagy of the viral silencing suppressor HCpro. Plant Physiol 176: 649–662 · DOI
  23. Hu H, Sun SC (2016) Ubiquitin signaling in immune responses. Cell Res 26: 457–483 · DOI
  24. Huang J, Brumell JH (2014) Bacteria‐autophagy interplay: a battle for survival. Nat Rev Microbiol 12: 101–114 · DOI
  25. Khan M, Seto D, Subramaniam R, Desveaux D (2018) Oh, the places they'll go! A survey of phytopathogen effectors and their host targets. Plant J 93: 651–663 · DOI
  26. Kim JG, Stork W, Mudgett MB (2013) Xanthomonas type III effector XopD desumoylates tomato transcription factor SlERF4 to suppress ethylene responses and promote pathogen growth. Cell Host Microbe 13: 143–154 · DOI
  27. Kim JG, Taylor KW, Hotson A, Keegan M, Schmelz EA, Mudgett MB (2008) XopD SUMO protease affects host transcription, promotes pathogen growth, and delays symptom development in xanthomonas‐infected tomato leaves. Plant Cell 20: 1915–1929 · DOI
  28. Kirkin V, Lamark T, Johansen T, Dikic I (2009) NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets. Autophagy 5: 732–733 · DOI
  29. Kliza K, Taumer C, Pinzuti I, Franz‐Wachtel M, Kunzelmann S, Stieglitz B, Macek B, Husnjak K (2017) Internally tagged ubiquitin: a tool to identify linear polyubiquitin‐modified proteins by mass spectrometry. Nat Methods 14: 504–512 · DOI
  30. Kovach ME, Elzer PH, Hill DS, Robertson GT, Farris MA, Roop 2nd RM, Peterson KM (1995) Four new derivatives of the broad‐host‐range cloning vector pBBR1MCS, carrying different antibiotic‐resistance cassettes. Gene 166: 175–176 · DOI
  31. Kubori T, Galan JE (2003) Temporal regulation of salmonella virulence effector function by proteasome‐dependent protein degradation. Cell 115: 333–342 · DOI
  32. Lal NK, Thanasuwat B, Huang PJ, Cavanaugh KA, Carter A, Michelmore RW, Dinesh‐Kumar SP (2020) Phytopathogen effectors use multiple mechanisms to manipulate plant autophagy. Cell Host Microbe 28: 558–571 · DOI
  33. Langin G, Gouguet P, Üstün S (2020) Microbial Effector proteins – a journey through the proteolytic landscape. Trends Microbiol 28: 523–535 · DOI
  34. Leary AY, Savage Z, Tumtas Y, Bozkurt TO (2019) Contrasting and emerging roles of autophagy in plant immunity. Curr Opin Plant Biol 52: 46–53 · DOI
  35. Lei L, Stevens DM, Coaker G (2020) Phosphorylation of the pseudomonas effector AvrPtoB by Arabidopsis SnRK2.8 is required for bacterial virulence. Mol Plant 13: 1513–1522 · DOI
  36. Lenz HD, Haller E, Melzer E, Kober K, Wurster K, Stahl M, Bassham DC, Vierstra RD, Parker JE, Bautor J et al (2011) Autophagy differentially controls plant basal immunity to biotrophic and necrotrophic pathogens. Plant J 66: 818–830 · DOI
  37. Lorenz C, Büttner D (2009) Functional characterization of the type III secretion ATPase HrcN from the plant pathogen Xanthomonas campestris pv. vesicatoria. J Bacteriol 191: 1414–1428 · DOI
  38. Lou L, Zhang P, Piao R, Wang Y (2019) Salmonella pathogenicity Island 1 (SPI‐1) and its complex regulatory network. Front Cell Infect Microbiol 9: 270 · DOI
  39. Marshall RS, Vierstra RD (2018) Autophagy: the master of bulk and selective recycling. Annu Rev Plant Biol 69: 173–208 · DOI
  40. Mesquita FS, Thomas M, Sachse M, Santos AJ, Figueira R, Holden DW (2012) The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. PLoS Pathog 8: e1002743 · DOI
  41. Minina EA, Moschou PN, Vetukuri RR, Sanchez‐Vera V, Cardoso C, Liu Q, Elander PH, Dalman K, Beganovic M, Lindberg Yilmaz J et al (2018) Transcriptional stimulation of rate‐limiting components of the autophagic pathway improves plant fitness. J Exp Bot 69: 1415–1432 · DOI
  42. Mostowy S (2013) Autophagy and bacterial clearance: a not so clear picture. Cell Microbiol 15: 395–402 · DOI
  43. Nagel MK, Kalinowska K, Vogel K, Reynolds GD, Wu Z, Anzenberger F, Ichikawa M, Tsutsumi C, Sato MH, Kuster B et al (2017) Arabidopsis SH3P2 is an ubiquitin‐binding protein that functions together with ESCRT‐I and the deubiquitylating enzyme AMSH3. Proc Natl Acad Sci USA 114: E7197–E7204 · DOI
  44. Nakagawa T, Kurose T, Hino T, Tanaka K, Kawamukai M, Niwa Y, Toyooka K, Matsuoka K, Jinbo T, Kimura T (2007) Development of series of gateway binary vectors, pGWBs, for realizing efficient construction of fusion genes for plant transformation. J Biosci Bioeng 104: 34–41 · DOI
  45. Pandey P, Leary AY, Tumtas Y, Savage Z, Dagvadorj B, Duggan C, Yuen EL, Sanguankiattichai N, Tan E, Khandare V et al (2021) An oomycete effector subverts host vesicle trafficking to channel starvation‐induced autophagy to the pathogen interface. Elife 10: e65285
  46. Pohl C, Dikic I (2019) Cellular quality control by the ubiquitin‐proteasome system and autophagy. Science 366: 818–822 · DOI · Paper page
  47. Schultink A, Qi T, Lee A, Steinbrenner AD, Staskawicz B (2017) Roq1 mediates recognition of the Xanthomonas and Pseudomonas effector proteins XopQ and HopQ1. Plant J 92: 787–795 · DOI
  48. Singer AU, Schulze S, Skarina T, Xu X, Cui H, Eschen‐Lippold L, Egler M, Srikumar T, Raught B, Lee J et al (2013) A pathogen type III effector with a novel E3 ubiquitin ligase architecture. PLoS Pathog 9: e1003121 · DOI
  49. Svenning S, Lamark T, Krause K, Johansen T (2011) Plant NBR1 is a selective autophagy substrate and a functional hybrid of the mammalian autophagic adapters NBR1 and p62/SQSTM1. Autophagy 7: 993–1010 · DOI
  50. Timilsina S, Potnis N, Newberry EA, Liyanapathiranage P, Iruegas‐Bocardo F, White FF, Goss EM, Jones JB (2020) Xanthomonas diversity, virulence and plant‐pathogen interactions. Nat Rev Microbiol 18: 415–427 · DOI
  51. Üstün S, Bartetzko V, Börnke F (2013) The Xanthomonas campestris type III effector XopJ targets the host cell proteasome to suppress salicylic‐acid mediated plant defence. PLoS Pathog 9: e1003427 · DOI
  52. Üstün S, Bartetzko V, Börnke F (2015) The Xanthomonas effector XopJ triggers a conditional hypersensitive response upon treatment of N. benthamiana leaves with salicylic acid. Front Plant Sci 6: 599 · DOI
  53. Üstün S, Börnke F (2014) Interactions of Xanthomonas type‐III effector proteins with the plant ubiquitin and ubiquitin‐like pathways. Front Plant Sci 5: 736
  54. Üstün S, Börnke F (2015) The Xanthomonas campestris type III effector XopJ proteolytically degrades proteasome subunit RPT6. Plant Physiol 168: 107–119 · DOI
  55. Üstün S, Hafrén A, Hofius D (2017) Autophagy as a mediator of life and death in plants. Curr Opin Plant Biol 40: 122–130 · DOI
  56. Üstün S, Hafrén A, Liu Q, Marshall RS, Minina EA, Bozhkov PV, Vierstra RD, Hofius D (2018) Bacteria exploit autophagy for proteasome degradation and enhanced virulence in plants. Plant Cell 30: 668–685 · DOI
  57. Üstün S, Hofius D (2018) Anti‐ and pro‐microbial roles of autophagy in plant‐bacteria interactions. Autophagy 14: 1465–1466 · DOI
  58. Üstün S, Konig P, Guttman DS, Börnke F (2014) HopZ4 from Pseudomonas syringae, a member of the HopZ type III effector family from the YopJ superfamily, inhibits the proteasome in plants. Mol Plant Microbe Interact 27: 611–623 · DOI
  59. Üstün S, Sheikh A, Gimenez‐Ibanez S, Jones A, Ntoukakis V, Börnke F (2016) The proteasome acts as a hub for plant immunity and is targeted by Pseudomonas type III effectors. Plant Physiol 172: 1941–1958 · DOI
  60. van Wijk SJ, Fiskin E, Putyrski M, Pampaloni F, Hou J, Wild P, Kensche T, Grecco HE, Bastiaens P, Dikic I (2012) Fluorescence‐based sensors to monitor localization and functions of linear and K63‐linked ubiquitin chains in cells. Mol Cell 47: 797–809 · DOI
  61. Yan Y, Wang P, He C, Shi H (2017) MeWRKY20 and its interacting and activating autophagy‐related protein 8 (MeATG8) regulate plant disease resistance in cassava. Biochem Biophys Res Commun 494: 20–26 · DOI
  62. Yang Y, Klionsky DJ (2020) Autophagy and disease: unanswered questions. Cell Death Differ 27: 858–871 · DOI
  63. Zeng H, Xie Y, Liu G, Lin D, He C, Shi H (2018) Molecular identification of GAPDHs in cassava highlights the antagonism of MeGAPCs and MeATG8s in plant disease resistance against cassava bacterial blight. Plant Mol Biol 97: 201–214 · DOI
  64. Zhang Y, Higashide W, Dai S, Sherman DM, Zhou D (2005) Recognition and ubiquitination of Salmonella type III effector SopA by a ubiquitin E3 ligase, HsRMA1. J Biol Chem 280: 38682–38688 · DOI
  65. Zheng YT, Shahnazari S, Brech A, Lamark T, Johansen T, Brumell JH (2009) The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol 183: 5909–5916 · DOI
  66. Zhou J, Wang J, Cheng Y, Chi YJ, Fan B, Yu JQ, Chen Z (2013) NBR1‐mediated selective autophagy targets insoluble ubiquitinated protein aggregates in plant stress responses. PLoS Genet 9: e1003196
  67. Zhuang X, Jiang L (2014) Autophagosome biogenesis in plants: roles of SH3P2. Autophagy 10: 704–705 · DOI
  68. Zhuang X, Wang H, Lam SK, Gao C, Wang X, Cai Y, Jiang L (2013) A BAR‐domain protein SH3P2, which binds to phosphatidylinositol 3‐phosphate and ATG8, regulates autophagosome formation in Arabidopsis. Plant Cell 25: 4596–4615 · DOI

Metadata

Authors
Leong, J. X., Raffeiner, M., Spinti, D., Langin, G., Franz‐Wachtel, M., Guzman, A. R., Kim, J., Pandey, P., Minina, A. E., Macek, B., Hafrén, A., Bozkurt, T. O., Mudgett, M. B., Börnke, F., Hofius, D., & Üstün, S.
Affiliations
  • University of Tübingen (DE)
  • Leibniz Institute of Vegetable and Ornamental Crops (DE)
  • Stanford University (US)
  • Imperial College London (GB)
  • Swedish University of Agricultural Sciences (SE)
  • University of Potsdam (DE)
Venue
The EMBO Journal
Published
2022-05-27
Volume
41
Issue
13
Pages
e110352-e110352
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W4281979571
Cited by
89
References
3
Citations by year
2026: 15 · 2025: 17 · 2024: 19 · 2023: 25 · 2022: 10
FWCI
9.78
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Epsilon Open Archive (Sveriges lantbruksuniversitet biblioteket (Swedish University of Agricultural Sciences)) (acceptedVersion)
  • publish.UP (University of Potsdam) (submittedVersion, cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (GZ, SFB1101, BO1961/5‐2, UE188/2‐1)
  • EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska‐Curie Actions (799433)
  • Svenska Forskningsrådet Formas (2017‐01596, 2016‐01044)
  • Vetenskapsrådet (2016‐04562, 2020‐05327)
  • UKRI | Biotechnology and Biological Sciences Research Council (BB/T006102/1)
  • NSF | BIO | Division of Integrative Organismal Systems (2026368)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Pathogenic Bacteria Studies
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant-Microbe Interactions and Immunity
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords
autophagy, xenophagy, plant-bacteria interactions, Xanthomonas campestris pv. vesicatoria, type III effectors, E3 ubiquitin ligase, NBR1, selective autophagy, plant defense
MeSH terms
Animals, Autophagy, Bacteria, Plant Diseases, Virulence Factors, Host-Pathogen Interactions

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