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  • Review Article
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Yeast viral killer toxins: lethality and self-protection

Nature Reviews Microbiology volume 4, pages 212–221 (2006)Cite this article

Key Points

  • The term 'killer strains' is used to describe yeast and fungal species that produce secreted toxins — known as 'killer toxins' — that have antimycotic activity. This killer phenotype can be associated with double-stranded (ds)RNA mycoviruses and linear dsDNA plasmids or can be chromosomally encoded. This article focuses on the killer phenotype associated with dsRNA viruses, with the emphasis on Saccharomyces cerevisiae.

  • In S. cerevisiae, three killer viruses have been identified — ScV-M1, ScV-M2 and ScV-M28 — each of which produces a specific killer toxin (K1, K2 and K28, respectively). In each case, the killer phenotype requires the presence of two different dsRNA viruses: an L-A helper virus and the toxin-coding killer virus. Besides K1, the K28 killer toxin is the most well studied.

  • The K28 toxin is initially translated in the yeast cytoplasm as a preprotoxin. Following processing and protoxin folding in the endoplasmic reticulum (ER) and late-Golgi compartment, the biologically active protein is secreted into the culture medium as an α/β heterodimer. The β-subunit of the K28 toxin precursor contains a classical ER-retention signal (HDEL) that is initially masked by a C-terminal arginine residue, allowing the toxin precursor to pass through the secretory pathway from the ER to the Golgi. The terminal arginine is removed by a processing reaction in the late-Golgi compartment and the HDEL sequence is then accessible for interaction with the HDEL receptor in the target cell.

  • The secreted mature toxin interacts with receptors in the cell wall and cytoplasmic membrane of sensitive yeast strains. To date, the membrane receptor for K28 has not been definitively identified, although current evidence suggests that it may be the cellular HDEL receptor Erd2p. The membrane receptor for toxin K1 has been identified — Kre1p, an O-glycosylated yeast cell-surface protein that is involved in β-1,6-glucan biosynthesis.

  • After endocytotic uptake and retrograde transport through the Golgi and ER to the cytosol, the K28 β-subunit is ubiquitinated and proteasomally degraded, and the α-subunit exerts its lethal effect in the nucleus, blocking DNA synthesis, causing cell-cycle arrest in early S phase. By contrast, ionophoric virus toxins, such as S. cerevisiae K1 and the Zygosaccharomyces bailii toxin zygocin, disrupt cytoplasmic membrane function by forming cation-selective ion channels.

  • A characteristic of the yeast-killer phenomenon is that toxin-producing yeast strains are immune to the toxin that they produce. A model is presented for K28 functional immunity, which suggests that mature, secreted K28 toxin — either self-produced or produced by other K28 killer cells — is taken up and transported through the Golgi and ER. Once in the cytosol, the mature toxin forms a complex with preprotoxin molecules that have not yet been imported into the ER, which can be ubiquitinated and then proteasomally degraded, protecting the cell from the lethal effects of the α-subunit.

Abstract

Since the discovery of toxin-secreting killer yeasts more than 40 years ago, research into this phenomenon has provided insights into eukaryotic cell biology and virus–host-cell interactions. This review focuses on the most recent advances in our understanding of the basic biology of virus-carrying killer yeasts, in particular the toxin-encoding killer viruses, and the intracellular processing, maturation and toxicity of the viral protein toxins. The strategy of using eukaryotic viral toxins to effectively penetrate and eventually kill a eukaryotic target cell will be discussed, and the cellular mechanisms of self-defence and protective immunity will also be addressed.

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Figure 1: Replication cycle of a toxin-encoding killer virus and its helper virus in the cytoplasm of a killer yeast.
Figure 2: Preprotoxin processing and toxin secretion in the yeast secretory pathway.
Figure 3: Endoplasmic-reticulum-to-cytosol retrotranslocation of the heterodimeric K28 toxin and lethal effect in the yeast nucleus.
Figure 4: Model of zygocin–membrane interaction.
Figure 5: Model of protective immunity in a K28-toxin-secreting killer yeast.

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References

  1. Bevan, E. A. & Makower, M. The physiological basis of the killer-character in yeast. in Genetics Today, XIth International Congress of Genetics Vol. 1 (ed. Geerts, S. J.) 202–203 (Pergamon Press, Oxford, 1963). The discovery of toxin-secreting yeast.

    Google Scholar 

  2. Bevan, E. A., Herring, A. J. & Mitchell, D. J. Preliminary characterisation of two species of dsRNA in yeast and their relationship to the “killer” character. Nature 245, 81–86 (1973). First report that links yeast dsRNA genomes to killer phenotype expression.

    Article  CAS  PubMed  Google Scholar 

  3. Herring, A. J. & Bevan, E. A. Virus-like particles associated with double-stranded RNA species found in killer and sensitive strains of the yeast Saccharomyces cerevisiae. J. Gen. Virol. 22, 387–394 (1974).

    Article  CAS  PubMed  Google Scholar 

  4. Magliani, W., Conti, S., Gerloni, M., Bertolotti, D. & Polonelli, L. Yeast killer systems. Clin. Microbiol. Rev. 10, 369–400 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bruenn, J. A. The double-stranded RNA viruses of Ustilago maydis and their killer toxins. in dsRNA Genetic Elements: Concepts and Applications in Agriculture, Forestry, and Medicine (ed. Tavantzis, S. M.) 109–124 (CRC Press, Boca Raton, 2002).

    Google Scholar 

  6. Schmitt, M. J. & Breinig, F. The viral killer system in yeast: from molecular biology to application. FEMS Microbiol. Rev. 26, 257–276 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Schmitt, M. J. & Neuhausen, F. Killer toxin-secreting double-stranded RNA mycoviruses in the yeasts Hanseniaspora uvarum and Zygosaccharomyces bailii. J. Virol. 68, 1765–1772 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Schmitt, M. J., Poravou, O., Trenz, K. & Rehfeldt, K. Unique double-stranded RNAs responsible for the anti-Candida activity of the yeast Hanseniaspora uvarum. J. Virol. 71, 8852–8855 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Zorg, J., Kilian, S. & Radler, F. Killer toxin producing strains of the yeasts Hanseniaspora uvarum and Pichia kluyveri. Arch. Microbiol. 149, 261–267 (1988).

    Article  Google Scholar 

  10. Radler, F., Herzberger, S., Schonig, I. & Schwarz, P. Investigation of a killer strain of Zygosaccharomyces bailii. J. Gen. Microbiol. 139, 495–500 (1993).

    Article  CAS  PubMed  Google Scholar 

  11. Park, C. M., Banerjee, N., Koltin, Y. & Bruenn, J. A. The Ustilago maydis virally encoded KP1 killer toxin. Mol. Microbiol. 20, 957–963 (1996).

    Article  CAS  PubMed  Google Scholar 

  12. Dawe, A. L. & Nuss, D. L. Hypoviruses and chestnut blight: exploiting viruses to understand and modulate fungal pathogenesis. Annu. Rev. Genet. 35, 1–29 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Bussey, H. K1 killer toxin, a pore-forming protein from yeast. Mol. Microbiol. 5, 2339–2243 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Schaffrath, R. & Meinhardt, F. Kluyveromyces lactis zymocin and related plasmid-encoded yeast killer toxins. in Topics in Current Genetics: Microbial Protein Toxins (eds Schmitt, M. J. & Schaffrath, R.) 133–155 (Springer-Verlag, Berlin Heidelberg, 2005).

    Google Scholar 

  15. Theisen, S., Molkenau, E. & Schmitt, M. J. Wicaltin, a new protein toxin secreted by the yeast Williopsis californica and its broad-spectrum antimycotic potential. J. Microbiol. Biotechnol. 10, 547–550 (2000).

    CAS  Google Scholar 

  16. Suzuki, C. Acidiphilic structure and killing mechanism of the Pichia farinosa killer toxin SMTK. in Topics in Current Genetics: Microbial Protein Toxins (eds Schmitt, M. J. & Schaffrath, R.) 189–214 (Springer-Verlag, Berlin Heidelberg, 2005).

    Google Scholar 

  17. Buck, K. W. Fungal Virology (CRC Press, Boca Raton, 1986).

    Google Scholar 

  18. Bruenn, J. A. Virus-like particles of yeast. Annu. Rev. Microbiol. 34, 49–68 (1980).

    Article  CAS  PubMed  Google Scholar 

  19. Hanes, S. D., Burn, V. E., Sturley, S. L., Tipper, D. J. & Bostian, K. A. Expression of a cDNA derived from the yeast killer preprotoxin gene: implications for processing and immunity. Proc. Natl Acad. Sci. USA 83, 1675–1679 (1986).

    Article  CAS  PubMed  Google Scholar 

  20. Dignard, D., Whiteway, M., Germain, D., Tessier, D. & Thomas, D. Y. Expression in yeast of a cDNA copy of the K2 killer toxin gene. Mol. Gen. Genet. 227, 127–136 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. Schmitt, M. J. & Tipper, D. J. K28, a unique double-stranded RNA killer virus of Saccharomyces cerevisiae. Mol. Cell. Biol. 10, 4807–4815 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schmitt, M. J. Cloning and expression of a cDNA copy of the viral K28 killer toxin gene in yeast. Mol. Gen. Genet. 246, 236–246 (1995).

    Article  CAS  PubMed  Google Scholar 

  23. Wickner, R. B. Double-stranded and single-stranded RNA viruses of Saccharomyces cerevisiae. Annu. Rev. Microbiol. 46, 347–375 (1992). Still an excellent review on yeast dsRNA virology.

    Article  CAS  PubMed  Google Scholar 

  24. Icho, T. & Wickner, R. B. The double-stranded RNA genome of yeast virus L-A encodes its own putative RNA polymerase by fusing two open reading frames. J. Biol. Chem. 264, 6716–6723 (1989).

    CAS  PubMed  Google Scholar 

  25. Dinman, J. D., Icho, T. & Wickner, R. B. A-1 ribosomal frameshift in a double-stranded RNA virus of yeast forms a gag–pol fusion protein. Proc. Natl Acad. Sci. USA 88, 174–178 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Fujimura, T., Ribas, J. C., Makhov, A. M. & Wickner, R. B. Pol of gag–pol fusion protein required for encapsidation of viral RNA of yeast L-A virus. Nature 359, 746–749 (1992).

    Article  CAS  PubMed  Google Scholar 

  27. Dinman, J. D. & Wickner, R. B. Translational maintenance of frame: mutants of Saccharomyces cerevisiae with altered-1 ribosomal frameshifting efficiencies. Genetics 136, 75–86 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Schmitt, M. J. & Tipper, D. J. Genetic analysis of maintenance and expression of L and M double-stranded RNAs from yeast killer virus K28. Yeast 8, 373–384 (1992).

    Article  CAS  PubMed  Google Scholar 

  29. Bussey, H., Vernet, T. & Sdicu, A. M. Mutual antagonism among killer yeasts: competition between K1 and K2 killers and a novel cDNA-based K1–K2 killer strain of Saccharomyces cerevisiae. Can. J. Microbiol. 34, 38–44 (1988).

    Article  CAS  PubMed  Google Scholar 

  30. Schmitt, M. J. & Schernikau, G. Construction of a cDNA-based K1/K2/K28 triple killer strain of Saccharomyces cerevisiae. Food Technol. Biotechnol. 35, 281–285 (1997).

    CAS  Google Scholar 

  31. Bruenn, J. A. Relationships among the positive strand and double-strand RNA viruses as viewed through their RNA-dependent RNA polymerases. Nucleic Acids Res. 19, 217–226 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cheng, R. H. et al. Fungal virus capsids, cytoplasmic compartments for the replication of double-stranded RNA, formed as icosahedral shells of asymmetric Gag dimers. J. Mol. Biol. 244, 255–258 (1994).

    Article  CAS  PubMed  Google Scholar 

  33. Naitow, H., Tang, J., Canady, M., Wickner, R. B. & Johnson, J. E. L-A virus at 3.4 Å resolution reveals particle architecture and mRNA decapping mechanism. Nature Struct. Biol. 9, 725–728 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. Tang, J. et al. The structural basis of recognition and removal of cellular mRNA 7-methyl G caps by a viral capsid protein: a unique viral response to host defense. J. Mol. Recognit. 18, 158–168 (2005).

    Article  CAS  PubMed  Google Scholar 

  35. Wickner, R. B. Double-stranded RNA viruses of Saccharomyces cerevisiae. Microbiol. Rev. 60, 250–265 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Wickner, R. B., Bussey, H., Fujimura, T. & Esteban, R. Viral RNA and the killer phenomenon of Saccharomyces. in The Mycota Vol. 2 (ed. Kück, U.) 211–226 (Springer, Berlin Heidelberg, 1995).

    Google Scholar 

  37. Caston, J. R. et al. Structure of L-A virus: a specialized compartment for the transcription and replication of double-stranded RNA. J. Cell Biol. 138, 975–985 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Esteban, R. & Wickner, R. B. Three different M1 RNA-containing viruslike particle types in Saccharomyces cerevisiae: in vitro M1 double-stranded RNA synthesis. Mol. Cell. Biol. 6, 1552–1561 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bostian, K. A., Sturgeon, J. A. & Tipper, D. J. Encapsidation of yeast killer double-stranded ribonucleic acids: dependence of M on L. J. Bacteriol. 143, 463–470 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Schmitt, M. J. & Tipper, D. J. Sequence of the M28 dsRNA: preprotoxin is processed to an α/β heterodimeric protein toxin. Virology 213, 341–351 (1995).

    Article  CAS  PubMed  Google Scholar 

  41. Fuller, R. S., Brake, A. & Thorner, J. Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent serine protease. Proc. Natl Acad. Sci. USA 86, 1434–1438 (1989).

    Article  CAS  PubMed  Google Scholar 

  42. Rockwell, N. C. & Thorner, J. W. The kindest cuts of all: crystal structures of Kex2 and furin reveal secrets of precursor processing. Trends Biochem. Sci. 29, 80–87 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. Riffer, F., Eisfeld, K., Breinig, F. & Schmitt, M. J. Mutational analysis of K28 preprotoxin processing in the yeast Saccharomyces cerevisiae. Microbiology 148, 1317–1328 (2002).

    Article  CAS  PubMed  Google Scholar 

  44. Eisfeld, K., Riffer, F., Mentges, J. & Schmitt, M. J. Endocytotic uptake and retrograde transport of a virally encoded killer toxin in yeast. Mol. Microbiol. 37, 926–940 (2000). First description of endocytosis and retrograde transport of a yeast killer toxin.

    Article  CAS  PubMed  Google Scholar 

  45. Townsley, F. M., Frigerio, G. & Pelham, H. R. Retrieval of HDEL proteins is required for growth of yeast cells. J. Cell Biol. 127, 21–28 (1994).

    Article  CAS  PubMed  Google Scholar 

  46. Kreitman, R. J. & Pastan, I. Importance of the glutamate residue of KDEL in increasing the cytotoxicity of Pseudomonas exotoxin derivatives and for increased binding to the KDEL receptor. Biochem. J. 307, 29–37 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lord, J. M. & Roberts, L. M. Toxin entry: retrograde transport through the secretory pathway. J. Cell Biol. 2, 733–736 (1998).

    Article  Google Scholar 

  48. Pelham, H. R. B., Roberts, L. M. & Lord, J. M. Toxin entry: how reversible is the secretory pathway? Trends Cell Biol. 2, 183–185 (1992).

    Article  CAS  PubMed  Google Scholar 

  49. Lord, J. M. et al. Retrograde transport of toxins accross the endoplasmic reticulum membrane. Biochem. Soc. Trans. 31, 1260–1262 (2003).

    Article  CAS  PubMed  Google Scholar 

  50. Lencer, W. I. & Tsai, B. The intracellular voyage of cholera toxin: going retro. Trends Biochem. Sci. 28, 639–645 (2003).

    Article  CAS  PubMed  Google Scholar 

  51. Snapp, E. L., Reinhart, G. A., Bogert, B. A., Lippincott-Schwartz, J. & Hedge, S. The organization of engaged and quiescent translocons in the endoplasmic reticulum of mammalian cells. J. Cell Biol. 164, 997–1007 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Beswick, V. et al. Expression, purification, and characterization of Sss1p, an essential component of the yeast Sec61p protein translocation complex. Protein Expr. Purif. 13, 423–432 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Pilon, M., Schekman, R. & Romisch, K. Sec61p mediates export of a misfolded secretory protein from the endoplasmic reticulum to the cytosol for degradation. EMBO J. 16, 4540–4548 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Plemper, R. K., Bohmler, S., Bordallo, J., Sommer, T. & Wolf, D. H. Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation. Nature 388, 891–895 (1997).

    Article  CAS  PubMed  Google Scholar 

  55. Tsai, B., Ye, Y. & Rapoport, T. A. Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nature Rev. Mol. Cell. Biol. 3, 246–255 (2002).

    Article  CAS  Google Scholar 

  56. Ellgaard, L. & Helenius, A. Quality control in the endoplasmic reticulum. Nature Rev. Mol. Cell. Biol. 4, 181–191 (2003).

    Article  CAS  Google Scholar 

  57. Wesche, J., Rapak, A. & Olsnes, S. Dependence of ricin toxicity on translocation of the toxin A-chain from the endoplasmic reticulum to the cytosol. J. Biol. Chem. 274, 34443–34449 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Schmitz, A., Herrgen, H., Winkeler, A. & Herzog, V. Cholera toxin is exported from microsomes by the Sec61p complex. J. Biol. Chem. 148, 1203–1212 (2000).

    CAS  Google Scholar 

  59. Koopman, J. et al. Export of antigenic peptides from the endoplasmic reticulum intersects with retrograde protein translocation through the Sec61p channel. Immunity 13, 117–127 (2000).

    Article  Google Scholar 

  60. Sommer, T. & Wolf, D. H. Endoplasmic reticulum degradation: reverse protein flow of no return. FASEB J. 11, 1227–1233 (1997).

    Article  CAS  PubMed  Google Scholar 

  61. Schmitt, M. & Radler, F. Molecular structure of the cell wall receptor for killer toxin KT28 in Saccharomyces cerevisiae. J. Bacteriol. 170, 2192–2196 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hutchins, K. & Bussey, H. Cell wall receptor for yeast killer toxin: involvement of 1,6-β-D-glucan. J. Bacteriol. 154, 161–169 (1983). First identification of the killer toxin K1 cell-wall receptor.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Boone, C., Sommer, S. S., Hensel, A. & Bussey, H. Yeast KRE genes provide evidence for a pathway of cell wall β-glucan assembly. J. Cell Biol. 110, 1833–1843 (1990).

    Article  CAS  PubMed  Google Scholar 

  64. Breinig, F., Tipper, D. J. & Schmitt, M. J. Kre1p, the plasma membrane receptor for the yeast K1 viral toxin. Cell 108, 395–405 (2002). First paper that identifies the K1 cytoplasmic membrane receptor.

    Article  CAS  PubMed  Google Scholar 

  65. Breinig, F., Schleinkofer, K. & Schmitt, M. J. Yeast Kre1p is GPI-anchored and involved in both cell wall assembly and architecture. Microbiology 150, 3209–3218 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Schmitt, M., Brendel, M., Schwarz, R. & Radler, F. Inhibition of DNA synthesis in Saccharomyces cerevisiae by yeast toxin K28. J. Gen. Microbiol. 135, 1529–1535 (1989).

    CAS  Google Scholar 

  67. Schmitt, M. J., Klavehn, P., Wang, J., Schonig, I. & Tipper, D. J. Cell cycle studies on the mode of action of yeast K28 killer toxin. Microbiology 142, 2655–2662 (1996).

    Article  CAS  PubMed  Google Scholar 

  68. Martinac, B. et al. Yeast K1 killer toxin forms ion channels in sensitive yeast spheroplasts and in artificial liposomes. Proc. Natl Acad. Sci. USA 87, 6228–6232 (1990). Important study on the ionophoric mode of action of K1 toxin.

    Article  CAS  PubMed  Google Scholar 

  69. Ahmed, A. et al. A molecular target for viral killer toxin: TOK1 potassium channels. Cell 99, 283–291 (1999).

    Article  CAS  PubMed  Google Scholar 

  70. Sesti, F., Shih, T. M., Nikolaeva, N. & Goldstein, S. A. Immunity to K1 killer toxin: internal TOK1 blockade. Cell 105, 637–644 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Bertl, A. et al. Characterization of potassium transport in wild-type and isogenic yeast strains carrying all combinations of trk1, trk2 and tok1 null mutations. Mol. Microbiol. 47, 767–780 (2003).

    Article  CAS  PubMed  Google Scholar 

  72. Page, N. et al. A Saccharomyces cerevisiae genome-wide mutant screen for altered sensitivity to K1 killer toxin. Genetics 163, 875–894 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Weiler, F. & Schmitt, M. J. Zygocin, a secreted antifungal toxin of the yeast Zygosaccharomyces bailii, and its effect on sensitive fungal cells. FEMS Yeast. Res. 3, 69–76 (2003).

    CAS  PubMed  Google Scholar 

  74. La Rocca, P., Biggin, P., Tieleman, D. P. & Sansom, M. S. Simulation studies of the interaction of antimicrobial peptides and lipid bilayers. Biochim. Biophys. Acta 1462, 185–200 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Tossi, A., Sandri, L. & Giangaspero, A. Amphiphatic, α-helical antimicrobial peptides. Biopolymers 55, 4–30 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Weiler, F., Rehfeldt, K., Bautz, F. & Schmitt, M. J. The Zygosaccharomyces bailii antifungal virus toxin zygocin: cloning and expression in a heterologous fungal host. Mol. Microbiol. 46, 1095–1105 (2002).

    Article  CAS  PubMed  Google Scholar 

  77. Sansom, M. S. Alamethicin and related peptaibols — model ion channels. Eur. Biophys. J. 22, 105–124 (1993).

    Article  CAS  PubMed  Google Scholar 

  78. Cafiso, D. S. Alamethicin: a peptide model for voltage gating and protein–membrane interactions. Annu. Rev. Biophys. Biomol. Struct. 23, 141–165 (1994).

    Article  CAS  PubMed  Google Scholar 

  79. Thevissen, K. et al. Fungal membrane responses induced by plant defensins and thionins. J. Biol. Chem. 271, 15018–15025 (1996).

    Article  CAS  PubMed  Google Scholar 

  80. Thevissen, K., Osborn, R. W., Acland, D. P. & Broekaert, W. F. Specific, high affinity binding sites for an antifungal plant defensin on Neurospora crassa hyphae and microsomal membranes. J. Biol. Chem. 272, 32176–32181 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389–395 (2002).

    Article  CAS  PubMed  Google Scholar 

  82. Peschel, A. et al. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine. J. Exp. Med. 193, 1067–1076 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. van den Hazel, H. B. et al. PDR16 and PDR17, two homologous genes of Saccharomyces cerevisiae, affect lipid biosynthesis and resistance to multiple drugs. J. Biol. Chem. 274, 1934–1941 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. Li, X. et al. Identification of a novel family of nonclassic yeast phosphatidylinositol transfer proteins whose function modulates phospholipase D activity and Sec14p-independent cell growth. Mol. Biol. Cell 11, 1989–2005 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Thevissen, K. et al. A gene encoding a sphingolipid biosynthesis enzyme determines the sensitivity of Saccharomyces cerevisiae to an antifungal plant defensin from dahlia (Dahlia merckii). Proc. Natl Acad. Sci. USA 97, 9531–9536 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Del Carratore, R. et al. Cell cycle and morphological alterations as indicative of apoptosis promoted by UV irradiation in S. cerevisiae. Mutat. Res. 513, 183–191 (2002).

    Article  CAS  PubMed  Google Scholar 

  87. Laun, P. et al. Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. Mol. Microbiol. 39, 1166–1173 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Ludovico, P., Sousa, M. J., Silva, M. T., Leao, C. & Corte-Real, M. Saccharomyces cerevisiae commits to a programmed cell death process in response to acetic acid. Microbiology 147, 2409–2415 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Madeo, F. et al. Oxygen stress: a regulator of apoptosis in yeast. J. Cell Biol. 145, 757–767 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Reiter, J., Herker, E., Madeo, F. & Schmitt, M. J. Viral killer toxins induce caspase-mediated apoptosis in yeast. J. Cell Biol. 168, 353–358 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Carmody, R. J. & Cotter, T. G. Signalling apoptosis: a radical approach. Redox Rep. 6, 77–90 (2001).

    Article  CAS  PubMed  Google Scholar 

  92. Madeo, F. et al. A caspase-related protease regulates apoptosis in yeast. Mol. Cell 9, 911–917 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Bussey, H., Sacks, W., Galley, D. & Saville, D. Yeast killer plasmid mutations affecting toxin secretion and activity and toxin immunity function. Mol. Cell. Biol. 2, 346–354 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Bussey, H., Saville, D., Greene, D., Tipper, D. J. & Bostian, K. A. Secretion of Saccharomyces cerevisiae killer toxin: processing of the glycosylated precursor. Mol. Cell. Biol. 3, 1362–1370 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sturley, S. L., Elliot, Q., LeVitre, J., Tipper, D. J. & Bostian, K. A. Mapping of functional domains within the Saccharomyces cerevisiae type 1 killer preprotoxin. EMBO J. 5, 3381–3389 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Boone, C., Bussey, H., Greene, D., Thomas, D. Y. & Vernet, T. Yeast killer toxin: site-directed mutations implicate the precursor protein as the immunity component. Cell 46, 105–113 (1986).

    Article  CAS  PubMed  Google Scholar 

  97. Bostian, K. A. et al. Sequence of the preprotoxin dsRNA gene of type I killer yeast: multiple processing events produce a two-component toxin. Cell 36, 741–751 (1984). First detailed analysis on pptox processing and maturation.

    Article  CAS  PubMed  Google Scholar 

  98. Zhu, Y. S., Kane, J., Zhang, X. Y., Zhang, M. & Tipper, D. J. Role of the γ component of preprotoxin in expression of the yeast K1 killer phenotype. Yeast 9, 251–266 (1993).

    Article  CAS  PubMed  Google Scholar 

  99. Douglas, C. M., Sturley, S. L. & Bostian, K. A. Role of protein processing, intracellular trafficking and endocytosis in production of and immunity to yeast killer toxin. Eur. J. Epidemiol. 4, 400–408 (1988).

    Article  CAS  PubMed  Google Scholar 

  100. Breinig, F., Sendzik, T., Eisfeld, K. & Schmitt, M. J. Dissecting toxin immunity in virus-infected killer yeast uncovers an intrinsic strategy of self protection. Proc. Natl Acad. Sci. USA (in the press).

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Acknowledgements

The authors thank all past and present members of the Schmitt laboratory for the many contributions over the years, and apologize to authors whose work could not be cited owing to space limitations. Work in the authors' laboratory that contributed to this review was continuously supported by various grants from the Deutsche Forschungsgemeinschaft.

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  1. Applied Molecular Biology, University of the Saarland, Saarbrücken, D-66041, Germany

    Manfred J. Schmitt & Frank Breinig

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  1. Manfred J. Schmitt
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  2. Frank Breinig
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Correspondence to Manfred J. Schmitt.

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DATABASES

Entrez Genome

ScV-M1

Entrez Genome Project

Candida albicans

Candida glabrata

Candida tropicalis

Escherichia coli

Kluyveromyces lactis

Pichia farinosa

Saccharomyces cerevisiae

Staphylococcus aureus

Ustilago maydis

FURTHER INFORMATION

Manfred J. Schmitt's homepage

Glossary

Virus-like particles

Yeast and fungal viruses that are transmitted in vivo by cell-to-cell passage and lack a natural extracellular route of infection.

Heterokaryon

Coexistence of two or more genetically different nuclei in a common cytoplasm.

Ribosomal frameshift event

A process used by many viral mRNAs that makes translating ribosomes change their reading frame by slipping one base in either the 5′ or 3′ direction. The frequency of ribosomal frameshift events is crucial for virus propagation and assembly, as it determines the stoichiometry of viral structural and enzymatic proteins.

Satellite viruses

Encapsidated viruses or virus-like particles composed of structural and enzymatic proteins that are encoded by a helper virus.

Conservative replication

Parental RNA strands remain associated, and the codogenic positive-strand RNA is made first, followed by negative-strand synthesis on the positive-strand RNA template.

Fluid-phase endocytosis

A receptor-independent process by which eukaryotic cells internalize portions of their cell surface to remove cargo such as proteins, lipids or solutes from the external environment. In yeast, accumulation of Lucifer yellow in the vacuole is used as a marker for fluid-phase endocytosis.

Coat proteins

Molecules that form a proteinaceous coating around vesicles that are involved in endoplasmic-reticulum and Golgi trafficking.

ER-associated degradation

A cellular quality-control system that ensures removal of misfolded and/or unassembled proteins from the endoplasmic-reticulum lumen and their subsequent elimination by the cytoplasmic ubiquitin–proteasome system.

Patch clamping

Technique whereby a small electrode tip is sealed onto a patch of cell membrane, making it possible to record the flow of current through individual ion channels or pores in the patch.

Spheroplasts

Yeast cells the cell wall of which has been enzymatically removed to increase the efficiencies of DNA transformation or virus-like-particle transfection.

Ergosterol

The main sterol in the cell membranes of yeast that is responsible, and essential, for structural and regulatory membrane features such as fluidity and permeability (equivalent to cholesterol in mammalian cells).

Nuclear-localization sequence

A short sequence in a protein, rich in basic residues, which acts as a signal for localization of the protein in the nucleus.

Importins

A family of proteins that transport macromolecules into the nucleus.

α-factor

One of two peptide hormones in Saccharomyces cerevisiae that are responsible for synchronized mating between yeast cells of opposite mating type.

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Schmitt, M., Breinig, F. Yeast viral killer toxins: lethality and self-protection. Nat Rev Microbiol 4, 212–221 (2006). https://doi.org/10.1038/nrmicro1347

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