1932

Abstract

Tc toxin complexes are virulence factors of many bacteria, including insect and human pathogens. Tc toxins are composed of three subunits that act together to perforate the host membrane, similar to a syringe, and translocate toxic enzymes into the host cell. The reactions of the toxic enzymes lead to deterioration and ultimately death of the cell. We review recent high-resolution structural and functional data that explain the mechanism of action of this type of bacterial toxin at an unprecedented level of molecular detail. We focus on the steps that are necessary for toxin activation and membrane permeation. This is where the largest conformational transitions appear. Furthermore, we compare the architecture and function of Tc toxins with those of anthrax toxin and vertebrate teneurin.

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2019-09-08
2024-04-17
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Literature Cited

  1. 1. 
    Blackburn MB, Martin PAW, Kuhar D, Farrar RR, Gundersen-Rindal DE 2011. The occurrence of Photorhabdus-like toxin complexes in Bacillus thuringiensis. PLOS ONE 6:3e18122
    [Google Scholar]
  2. 2. 
    Bowen D, Rocheleau TA, Blackburn M, Andreev O, Golubeva E et al. 1998. Insecticidal toxins from the bacterium Photorhabdus luminescens. Science 280:53722129–32First description of Tc complexes in P. luminescens and their identification as toxins.
    [Google Scholar]
  3. 3. 
    Bowen DJ, Ensign JC. 1998. Purification and characterization of a high-molecular-weight insecticidal protein complex produced by the entomopathogenic bacterium Photorhabdus luminescen. s. Appl. Environ. Microbiol 64:83029–35
    [Google Scholar]
  4. 4. 
    Bresolin G, Morgan JAW, Ilgen D, Scherer S, Fuchs TM 2006. Low temperature-induced insecticidal activity of Yersinia enterocolitica. Mol. Microbiol 59:2503–12
    [Google Scholar]
  5. 5. 
    Bresolin G, Neuhaus K, Scherer S, Fuchs TM 2006. Transcriptional analysis of long-term adaptation of Yersinia enterocolitica to low-temperature growth. J. Bacteriol. 188:82945–58
    [Google Scholar]
  6. 6. 
    Brown MJ, Thoren KL, Krantz BA 2011. Charge requirements for proton gradient-driven translocation of anthrax toxin. J. Biol. Chem. 286:2623189–99
    [Google Scholar]
  7. 7. 
    Busby JN, Landsberg MJ, Simpson RM, Jones SA, Hankamer B et al. 2012. Structural analysis of Chi1 chitinase from Yen-Tc: the multisubunit insecticidal ABC toxin complex of Yersinia entomophaga. J. Mol. Biol 415:2359–71
    [Google Scholar]
  8. 8. 
    Busby JN, Panjikar S, Landsberg MJ, Hurst MRH, Lott JS 2013. The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device. Nature 501:7468547–50First structure of TcB-TcC showing that it forms a cocoon that encapsulates the toxic enzyme.
    [Google Scholar]
  9. 9. 
    Choe S, Bennett MJ, Fujii G, Curmi PM, Kantardjieff KA et al. 1992. The crystal structure of diphtheria toxin. Nature 357:6375216–22
    [Google Scholar]
  10. 10. 
    Ciche TA, Kim K-S, Kaufmann-Daszczuk B, Nguyen KCQ, Hall DH 2008. Cell invasion and matricide during Photorhabdus luminescens transmission by Heterorhabditis bacteriophora nematodes. Appl. Environ. Microbiol. 74:82275–87
    [Google Scholar]
  11. 11. 
    Cioci G, Mitchell EP, Chazalet V, Debray H, Oscarson S et al. 2006. Beta-propeller crystal structure of Psathyrella velutina lectin: an integrin-like fungal protein interacting with monosaccharides and calcium. J. Mol. Biol. 357:51575–91
    [Google Scholar]
  12. 12. 
    Dow JA. 1984. Extremely high pH in biological systems: a model for carbonate transport. Am. J. Physiol. 246:4 Part 2R633–36
    [Google Scholar]
  13. 13. 
    Duchaud E, Rusniok C, Frangeul L, Buchrieser C, Givaudan A et al. 2003. The genome sequence of the entomopathogenic bacterium Photorhabdus luminescens. Nat. Biotechnol 21:111307–13
    [Google Scholar]
  14. 14. 
    Dunn BM. 2001. Overview of pepsin-like aspartic peptidases. Curr. Protoc. Protein Sci. 25:21.3–21.3.6
    [Google Scholar]
  15. 15. 
    Efremov RG, Gatsogiannis C, Raunser S 2017. Lipid nanodiscs as a tool for high-resolution structure determination of membrane proteins by single-particle cryo-EM. Meth. Enzymol. 594:1–30
    [Google Scholar]
  16. 16. 
    Erickson DL, Waterfield NR, Vadyvaloo V, Long D, Fischer ER et al. 2007. Acute oral toxicity of Yersinia pseudotuberculosis to fleas: implications for the evolution of vector-borne transmission of plague. Cell. Microbiol. 9:112658–66
    [Google Scholar]
  17. 17. 
    Ernst K, Schmid J, Beck M, Hägele M, Hohwieler M et al. 2017. Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells. Sci. Rep. 7:12724
    [Google Scholar]
  18. 18. 
    Farmer JJ, Jorgensen JH, Grimont PA, Akhurst RJ, Poinar GO et al. 1989. Xenorhabdus luminescens (DNA hybridization group 5) from human clinical specimens. J. Clin. Microbiol. 27:71594–600
    [Google Scholar]
  19. 19. 
    Feld GK, Brown MJ, Krantz BA 2012. Ratcheting up protein translocation with anthrax toxin. Protein Sci 21:5606–24
    [Google Scholar]
  20. 20. 
    Feld GK, Thoren KL, Kintzer AF, Sterling HJ, Tang II et al. 2010. Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers. Nat. Struct. Mol. Biol. 17:111383–90
    [Google Scholar]
  21. 21. 
    Ferralli J, Tucker RP, Chiquet-Ehrismann R 2018. The teneurin C-terminal domain possesses nuclease activity and is apoptogenic. Biol. Open 7:3bio031765
    [Google Scholar]
  22. 22. 
    ffrench-Constant R, Waterfield N. 2005. An ABC guide to the bacterial toxin complexes. Adv. Appl. Microbiol. 58:169–83Comprehensive review that compares the presence of different Tc genes in different bacteria.
    [Google Scholar]
  23. 23. 
    ffrench-Constant R, Waterfield N, Daborn P, Joyce S, Bennett H et al. 2003. Photorhabdus: towards a functional genomic analysis of a symbiont and pathogen. FEMS Microbiol. Rev. 26:5433–56
    [Google Scholar]
  24. 24. 
    ffrench-Constant RH, Bowen DJ. 2000. Novel insecticidal toxins from nematode-symbiotic bacteria. Cell. Mol. Life Sci. 57:5828–33
    [Google Scholar]
  25. 25. 
    ffrench-Constant RH, Waterfield N, Burland V, Perna NT, Daborn PJ et al. 2000. A genomic sample sequence of the entomopathogenic bacterium Photorhabdus luminescens W14: potential implications for virulence. Appl. Environ. Microbiol. 66:83310–29Report on sequences of P. luminescens genomic samples, showing the presence of different tc genes.
    [Google Scholar]
  26. 26. 
    Fuchs TM, Bresolin G, Marcinowski L, Schachtner J, Scherer S 2008. Insecticidal genes of Yersinia spp.: taxonomical distribution, contribution to toxicity towards Manduca sexta and Galleria mellonella, and evolution. BMC Microbiol 8:1214
    [Google Scholar]
  27. 27. 
    Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN et al. 2017. Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. Science 357:6348273–79
    [Google Scholar]
  28. 28. 
    Gatsogiannis C, Lang AE, Meusch D, Pfaumann V, Hofnagel O et al. 2013. A syringe-like injection mechanism in Photorhabdus luminescens toxins. Nature 495:7442520–23Low-resolution structures of different states of a Tc toxin, showing its mechanism of action.
    [Google Scholar]
  29. 29. 
    Gatsogiannis C, Merino F, Prumbaum D, Roderer D, Leidreiter F et al. 2016. Membrane insertion of a Tc toxin in near-atomic detail. Nat. Struct. Mol. Biol. 23:10884–90Comprehensive functional and structural study of Tc toxin membrane insertion.
    [Google Scholar]
  30. 30. 
    Gatsogiannis C, Merino F, Roderer D, Balchin D, Schubert E et al. 2018. Tc toxin activation requires unfolding and refolding of a β-propeller. Nature 563:209–13Comprehensive functional and structural study of Tc holotoxin assembly and activation.
    [Google Scholar]
  31. 31. 
    Gerrard J, Waterfield N, Vohra R, ffrench-Constant R 2004. Human infection with Photorhabdus asymbiotica: An emerging bacterial pathogen. Microbes Infection 6:2229–37
    [Google Scholar]
  32. 32. 
    Hares MC, Hinchliffe SJ, Strong PCR, Eleftherianos I, Dowling AJ et al. 2008. The Yersinia pseudotuberculosis and Yersinia pestis toxin complex is active against cultured mammalian cells. Microbiology 154:Part 113503–17
    [Google Scholar]
  33. 33. 
    Hey TD, Schleper AD, Bevan SA, Bintrim SB, Mitchell JC et al. 2009. Mixing and matching TC proteins for pest control US Patent 7,491,698 B2
  34. 34. 
    Hill CW, Sandt CH, Vlazny DA 1994. Rhs elements of Escherichia coli: a family of genetic composites each encoding a large mosaic protein. Mol. Microbiol. 12:6865–71
    [Google Scholar]
  35. 35. 
    Hinchliffe SJ, Hares MC. 2010. Insecticidal toxins from the Photorhabdus and Xenorhabdus bacteria. Open Toxinol. J. 3:83–100
    [Google Scholar]
  36. 36. 
    Hurst MR, Glare TR, Jackson TA, Ronson CW 2000. Plasmid-located pathogenicity determinants of Serratia entomophila, the causal agent of amber disease of grass grub, show similarity to the insecticidal toxins of Photorhabdus luminescens. J. Bacteriol 182:185127–38
    [Google Scholar]
  37. 37. 
    Hurst MRH, Jones SA, Binglin T, Harper LA, Jackson TA, Glare TR 2011. The main virulence determinant of Yersinia entomophaga MH96 is a broad-host-range toxin complex active against insects. J. Bacteriol. 193:81966–80
    [Google Scholar]
  38. 38. 
    Iyer LM, Zhang D, Rogozin IB, Aravind L 2011. Evolution of the deaminase fold and multiple origins of eukaryotic editing and mutagenic nucleic acid deaminases from bacterial toxin systems. Nucleic Acids Res 39:229473–97
    [Google Scholar]
  39. 39. 
    Jackson VA, Meijer DH, Carrasquero M, van Bezouwen LS, Lowe ED et al. 2018. Structures of teneurin adhesion receptors reveal an ancient fold for cell-cell interaction. Nat. Commun. 9:11079
    [Google Scholar]
  40. 40. 
    Jiang J, Pentelute BL, Collier RJ, Zhou ZH 2015. Atomic structure of anthrax protective antigen pore elucidates toxin translocation. Nature 521:7553545–49
    [Google Scholar]
  41. 41. 
    Jones SA, Hurst MRH. 2016. Purification of the Yersinia entomophaga Yen-TC toxin complex using size exclusion chromatography. Methods Mol. Biol. 1477:Chapter 439–48
    [Google Scholar]
  42. 42. 
    Kaya HK, Gaugler R. 1993. Entomopathogenic nematodes. Annu. Rev. Entomol. 38:181–206
    [Google Scholar]
  43. 43. 
    Krantz BA, Finkelstein A, Collier RJ 2006. Protein translocation through the anthrax toxin transmembrane pore is driven by a proton gradient. J. Mol. Biol. 355:5968–79
    [Google Scholar]
  44. 44. 
    Krantz BA, Melnyk RA, Zhang S, Juris SJ, Lacy DB et al. 2005. A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore. Science 309:5735777–81
    [Google Scholar]
  45. 45. 
    Kuehlbrandt W. 2014. The resolution revolution. Science 343:61781443–44
    [Google Scholar]
  46. 46. 
    Landsberg MJ, Jones SA, Rothnagel R, Busby JN, Marshall SDG et al. 2011. 3D structure of the Yersinia entomophaga toxin complex and implications for insecticidal activity. PNAS 108:5120544–49
    [Google Scholar]
  47. 47. 
    Lang AE, Ernst K, Lee H, Papatheodorou P, Schwan C et al. 2014. The chaperone Hsp90 and PPIases of the cyclophilin and FKBP families facilitate membrane translocation of Photorhabdus luminescens ADP-ribosyltransferases. Cell. Microbiol. 16:4490–503
    [Google Scholar]
  48. 48. 
    Lang AE, Konukiewitz J, Aktories K, Benz R 2013. TcdA1 of Photorhabdus luminescens: electrophysiological analysis of pore formation and effector binding. Biophys. J. 105:2376–84
    [Google Scholar]
  49. 49. 
    Lang AE, Schmidt G, Schlosser A, Hey TD, Larrinua IM et al. 2010. Photorhabdus luminescens toxins ADP-ribosylate actin and RhoA to force actin clustering. Science 327:59691139–42Functional proof that two HVRs of P. luminescens act as ADP-ribosyltransferases, resulting in actin clustering.
    [Google Scholar]
  50. 50. 
    Lee SC, Stoilova-Mcphie S, Baxter L, Fulop V, Henderson J et al. 2007. Structural characterisation of the insecticidal toxin XptA1, reveals a 1.15 MDa tetramer with a cage-like structure. J. Mol. Biol. 366:51558–68
    [Google Scholar]
  51. 51. 
    Lehane MJ. 1997. Peritrophic matrix structure and function. Annu. Rev. Entomol. 42:525–50
    [Google Scholar]
  52. 52. 
    Li J, Shalev-Benami M, Sando R, Jiang X, Kibrom A et al. 2018. Structural basis for teneurin function in circuit-wiring: a toxin motif at the synapse. Cell 173:3735–48.e15Structure of a teneurin, showing that teneurins are structurally but not functionally similar to TcB-TcC.
    [Google Scholar]
  53. 53. 
    Merino F, Raunser S. 2017. Electron cryo-microscopy as a tool for structure-based drug development. Angew. Chem. Int. Ed. Engl. 56:112846–60
    [Google Scholar]
  54. 54. 
    Ménétrey J, Flatau G, Stura EA, Charbonnier JB, Gas F et al. 2002. NAD binding induces conformational changes in Rho ADP-ribosylating Clostridium botulinum C3 exoenzyme. J. Biol. Chem. 277:3430950–57
    [Google Scholar]
  55. 55. 
    Meusch D, Gatsogiannis C, Efremov RG, Lang AE, Hofnagel O et al. 2014. Mechanism of Tc toxin action revealed in molecular detail. Nature 508:749461–65First high-resolution structure of TcA, explaining the role of its individual domains.
    [Google Scholar]
  56. 56. 
    Milstead JE. 1979. Heterorhabditis bacteriophora as a vector for introducing its associated bacterium into the hemocoel of Galleria mellonella larvae. J. Invertebr. Pathol. 33:3324–27
    [Google Scholar]
  57. 57. 
    Moriya T, Saur M, Stabrin M, Merino F, Voicu H et al. 2017. High-resolution single particle analysis from electron cryo-microscopy images using SPHIRE. J. Vis. Exp. 2017:123e55448
    [Google Scholar]
  58. 58. 
    Murphy JR. 2011. Mechanism of diphtheria toxin catalytic domain delivery to the eukaryotic cell cytosol and the cellular factors that directly participate in the process. Toxins 3:3294–308
    [Google Scholar]
  59. 59. 
    Olsnes S, Moskaug JO, Stenmark H, Sandvig K 1988. Diphtheria toxin entry: protein translocation in the reverse direction. Trends Biochem. Sci. 13:9348–51
    [Google Scholar]
  60. 60. 
    Petosa C, Collier RJ, Klimpel KR, Leppla SH, Liddington RC 1997. Crystal structure of the anthrax toxin protective antigen. Nature 385:6619833–38
    [Google Scholar]
  61. 61. 
    Pinheiro VB, Ellar DJ. 2007. Expression and insecticidal activity of Yersinia pseudotuberculosis and Photorhabdus luminescens toxin complex proteins. Cell. Microbiol. 9:102372–80
    [Google Scholar]
  62. 62. 
    Puchades C, Rampello AJ, Shin M, Giuliano CJ, Wiseman RL et al. 2017. Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing. Science 358:6363eaao0464
    [Google Scholar]
  63. 63. 
    Quentin D, Ahmad S, Shanthamoorthy P, Mougous JD, Whitney JC, Raunser S 2018. Mechanism of loading and translocation of type VI secretion system effector Tse6. Nat. Microbiol. 3:101142–52
    [Google Scholar]
  64. 64. 
    Rangel LI, Henkels MD, Shaffer BT, Walker FL, Davis EW et al. 2016. Characterization of toxin complex gene clusters and insect toxicity of bacteria representing four subgroups of Pseudomonas fluorescens. PLOS ONE 11:8e0161120
    [Google Scholar]
  65. 65. 
    Ren X-M, Li D-F, Jiang S, Lan X-Q, Hu Y et al. 2015. Structural basis of specific recognition of non-reducing terminal N-acetylglucosamine by an Agrocybe aegerita lectin. PLOS ONE 10:6e0129608
    [Google Scholar]
  66. 66. 
    Rubin BP, Tucker RP, Martin D, Chiquet-Ehrismann R 1999. Teneurins: a novel family of neuronal cell surface proteins in vertebrates, homologous to the Drosophila pair-rule gene product Ten-m. Dev. Biol. 216:1195–209
    [Google Scholar]
  67. 67. 
    Sergeant M, Jarrett P, Ousley M, Morgan JAW 2003. Interactions of insecticidal toxin gene products from Xenorhabdus nematophilus PMFI296. Appl. Environ. Microbiol. 69:63344–49
    [Google Scholar]
  68. 68. 
    Sheets J, Aktories K. 2017. Insecticidal toxin complexes from Photorhabdus luminescens. Curr. Top. Microbiol. Immunol 402:83–23
    [Google Scholar]
  69. 69. 
    Sheets JJ, Hey TD, Fencil KJ, Burton SL, Ni W et al. 2011. Insecticidal toxin complex proteins from Xenorhabdus nematophilus: structure and pore formation. J. Biol. Chem. 286:2622742–49
    [Google Scholar]
  70. 70. 
    Simon NC, Aktories K, Barbieri JT 2014. Novel bacterial ADP-ribosylating toxins: structure and function. Nat. Rev. Microbiol. 12:9599–611
    [Google Scholar]
  71. 71. 
    Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE 1996. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 274:52941859–66
    [Google Scholar]
  72. 72. 
    Sparks MA, Crowley SD, Gurley SB, Mirotsou M, Coffman TM 2014. Classical renin-angiotensin system in kidney physiology. Compr. Physiol. 4:31201–28
    [Google Scholar]
  73. 73. 
    Spinner JL, Jarrett CO, LaRock DL, Miller SI, Collins CM, Hinnebusch BJ 2012. Yersinia pestis insecticidal-like toxin complex (Tc) family proteins: characterization of expression, subcellular localization, and potential role in infection of the flea vector. BMC Microbiol 12:1296
    [Google Scholar]
  74. 74. 
    Trought T, Jackson TA, French RA 1982. Incidence and transmission of a disease of grass grub (Costelytra zealandica) in Canterbury. N.Z. J. Exp. Agric. 10:179–82
    [Google Scholar]
  75. 75. 
    Vadyvaloo V, Jarrett C, Sturdevant DE, Sebbane F, Hinnebusch BJ 2010. Transit through the flea vector induces a pretransmission innate immunity resistance phenotype in Yersinia pestis. PLOS Pathog 6:2e1000783
    [Google Scholar]
  76. 76. 
    Waterfield N, Hares M, Hinchliffe S, Wren B, ffrench-Constant R 2007. The insect toxin complex of Yersinia. Adv. Exp. Med. Biol 603:Chapter 22247–57
    [Google Scholar]
  77. 77. 
    Waterfield N, Hares M, Yang G, Dowling A, ffrench-Constant R 2005. Potentiation and cellular phenotypes of the insecticidal Toxin complexes of Photorhabdus bacteria. Cell. Microbiol 7:3373–82
    [Google Scholar]
  78. 78. 
    Waterfield NR, Ciche T, Clarke D 2009. Photorhabdus and a host of hosts. Annu. Rev. Microbiol. 63:557–74
    [Google Scholar]
  79. 79. 
    Wiedemann N, Pfanner N. 2017. Mitochondrial machineries for protein import and assembly. Annu. Rev. Biochem. 86:685–714
    [Google Scholar]
  80. 80. 
    Wilkinson P, Waterfield NR, Crossman L, Corton C, Sanchez-Contreras M et al. 2009. Comparative genomics of the emerging human pathogen Photorhabdus asymbiotica with the insect pathogen Photorhabdus luminescens. BMC Genom 10:1302
    [Google Scholar]
  81. 81. 
    Xu Z, Horwich AL, Sigler PB 1997. The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex. Nature 388:6644741–50
    [Google Scholar]
  82. 82. 
    Yamashita K, Kawai Y, Tanaka Y, Hirano N, Kaneko J et al. 2011. Crystal structure of the octameric pore of staphylococcal γ-hemolysin reveals the β-barrel pore formation mechanism by two components. PNAS 108:4217314–19
    [Google Scholar]
  83. 83. 
    Yang G, Waterfield NR. 2013. The role of TcdB and TccC subunits in secretion of the Photorhabdus Tcd toxin complex. PLOS Pathog 9:10e1003644
    [Google Scholar]
  84. 84. 
    Young JAT, Collier RJ. 2007. Anthrax toxin: receptor binding, internalization, pore formation, and translocation. Annu. Rev. Biochem. 76:243–65
    [Google Scholar]
  85. 85. 
    Zhan Z, Qiu X, Han R 2016. Horizontal transfer of the C-termini of tccC genes in Photorhabdus and Xenorhabdus. Genes Genom 38:8685–92
    [Google Scholar]
  86. 86. 
    Zhang S, Finkelstein A, Collier RJ 2004. Evidence that translocation of anthrax toxin's lethal factor is initiated by entry of its N terminus into the protective antigen channel. PNAS 101:4816756–61
    [Google Scholar]
  87. 87. 
    Zhu X, Zhao X, Burkholder WF, Gragerov A, Ogata CM et al. 1996. Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272:52681606–14
    [Google Scholar]
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