Acta Neuropathologica

, 112:1 | Cite as

Koch’s postulates and infectious proteins

Hypothesis Paper

Abstract

Koch’s postulates were formulated in the late nineteenth century as guidelines for establishing that microbes cause specific diseases. Because the rules were developed for living agents—particularly bacteria—their applicability to inanimate pathogens such as viruses and infectious proteins has been problematic. The unorthodox mechanism by which prion diseases are transmitted, involving specific physicochemical characteristics of the protein as well as susceptibility traits of the host, has made these disorders refractory to analysis within the context of the original Koch’s postulates. In addition, evidence is accumulating that other proteopathies, such as AA amyloidosis, apolipoprotein AII amyloidosis, and cerebral Aβ amyloidosis, can be induced in vulnerable recipients by cognate proteinaceous agents. In light of the salient differences in the mode of disease-transmission by microbes and proteins, we propose modifications of Koch’s postulates that will specifically accommodate presumed infectious proteins.

Keywords

Alzheimer’s disease Amyloid Apolipoprotein AII Conformational disease Prion 

References

  1. 1.
    Aguzzi A, Polymenidou M (2004) Mammalian prion biology: one century of evolving concepts. Cell 116:313–327PubMedCrossRefGoogle Scholar
  2. 2.
    Brock TD (1999) Robert Koch: a life in medicine and bacteriology. American Society of Microbiology Press, WashingtonGoogle Scholar
  3. 3.
    Carrell RW, Lomas DA (2002) Alpha1-antitrypsin deficiency—a model for conformational diseases. N Engl J Med 346:45–53PubMedCrossRefGoogle Scholar
  4. 4.
    Castilla J, Saa P, Hetz C, Soto C (2005) In vitro generation of infectious scrapie prions. Cell 121:195–206PubMedCrossRefGoogle Scholar
  5. 5.
    Caughey B, Lansbury PT (2003) Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci 26:267–298PubMedCrossRefGoogle Scholar
  6. 6.
    Chesebro B (2003) Introduction to the transmissible spongiform encephalopathies or prion diseases. Br Med Bull 66:1–20PubMedCrossRefGoogle Scholar
  7. 7.
    Chesebro B, Trifilo M, Race R, Meade-White K, Teng C, LaCasse R, Raymond L, Favara C, Baron G, Priola S, Caughey B, Masliah E, Oldstone M (2005) Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308:1420–1421CrossRefGoogle Scholar
  8. 8.
    Chien P, Weissman JS, DePace AH (2004) Emerging principles of conformation-based prion inheritance. Annu Rev Biochem 73:617–656PubMedCrossRefGoogle Scholar
  9. 9.
    Dobson CM (2002) Getting out of shape. Nature 418:729–730PubMedCrossRefGoogle Scholar
  10. 10.
    Dobson CM (2005) Structural biology: prying into prions. Nature 435:747–749PubMedCrossRefGoogle Scholar
  11. 11.
    Dzwolak W, Grudzielanek S, Smirnovas V, Ravindra R, Nicolini C, Jansen R, Loksztejn A, Porowski S, Winter R (2005) Ethanol-perturbed amyloidogenic self-assembly of insulin: looking for origins of amyloid strains. Biochemistry 44:8948–8958PubMedCrossRefGoogle Scholar
  12. 12.
    Evans AS (1991) Causation and disease: effect of technology on postulates of causation. Yale J Biol Med 64:513–528PubMedGoogle Scholar
  13. 13.
    Evans AS (1976) Causation and disease: the Henle-Koch postulates revisited. Yale J Biol Med 49:175–195PubMedGoogle Scholar
  14. 14.
    Falkow S (2004) Molecular Koch’s postulates applied to bacterial pathogenicity—a personal recollection 15 years later. Nat Rev Microbiol 2:67–72PubMedCrossRefGoogle Scholar
  15. 15.
    Fu X, Korenaga T, Fu L, Xing Y, Guo Z, Matsushita T, Hosokawa M, Naiki H, Baba S, Kawata Y, Ikeda S, Ishihara T, Mori M, Higuchi K (2004) Induction of AApoAII amyloidosis by various heterogeneous amyloid fibrils. FEBS Lett 563:179–184PubMedCrossRefGoogle Scholar
  16. 16.
    Gajdusek DC (1994) Spontaneous generation of infectious nucleating amyloids in the transmissible and nontransmissible cerebral amyloidoses. Mol Neurobiol 8:1–13PubMedCrossRefGoogle Scholar
  17. 17.
    Hardy J (2005) Expression of normal sequence pathogenic proteins for neurodegeneration contributes to disease risk: “Permissive templating” as a general disease mechanism of neurodegeneration. Biochem Soc Trans 33:578–581PubMedCrossRefGoogle Scholar
  18. 18.
    Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356PubMedCrossRefGoogle Scholar
  19. 19.
    Heikenwalder M, Zeller N, Seeger H, Prinz M, Klohn PC, Schwarz P, Ruddle NH, Weissmann C, Aguzzi A (2005) Chronic lymphocytic inflammation specifies the organ tropism of prions. Science 307:1107–1110PubMedCrossRefGoogle Scholar
  20. 20.
    Jones EM, Surewicz WK (2005) Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids. Cell 121:63–72PubMedCrossRefGoogle Scholar
  21. 21.
    Jones EM, Surewicz K, Surewicz WK (2006) Role of N-terminal familial mutations in prion protein fibrillization and prion amyloid propagation in vitro. J Biol Chem 281:8190–8196PubMedCrossRefGoogle Scholar
  22. 22.
    Kakizuka A (1998) Protein precipitation: a common etiology in neurodegenerative disorders? Trends Genet 14:396–402PubMedCrossRefGoogle Scholar
  23. 23.
    Krishnan R, Lindquist SL (2005) Structural insights into a yeast prion illuminate nucleation and strain diversity. Nature 435:765–772PubMedCrossRefGoogle Scholar
  24. 24.
    Legname G, Baskakov IV, Nguyen HO, Riesner D, Cohen FE, DeArmond SJ, Prusiner SB (2004) Synthetic mammalian prions. Science 305:673–676PubMedCrossRefGoogle Scholar
  25. 25.
    Legname G, Nguyen HO, Baskakov IV, Cohen FE, DeArmond SJ, Prusiner SB (2005) Strain-specified characteristics of mouse synthetic prions. Proc Natl Acad Sci USA 102:2168–2173PubMedCrossRefGoogle Scholar
  26. 26.
    Loeffler F (1884) Untersuchungen über die Bedeutung der Mikroorganismen für die Entstehung der Diptherie beim Menschen, bei der Taube und beim Kalbe. Mitth. a.d. kaiserl. Gesundheitsampte Ii, pp 421–499Google Scholar
  27. 27.
    Lundmark K, Westermark GT, Olsen A, Westermark P (2005) Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: cross-seeding as a disease mechanism. Proc Natl Acad Sci USA 102:6098–6102PubMedCrossRefGoogle Scholar
  28. 28.
    Nelson R, Sawaya MR, Balbirnie M, Madsen AO, Riekel C, Grothe R, Eisenberg D (2005) Structure of the cross-beta spine of amyloid-like fibrils. Nature 435:773–778PubMedCrossRefGoogle Scholar
  29. 29.
    O’Nuallain B, Williams AD, Westermark P, Wetzel R (2004) Seeding specificity in amyloid growth induced by heterologous fibrils. J Biol Chem 279:17490–17490PubMedCrossRefGoogle Scholar
  30. 30.
    Petkova AT, Leapman RD, Guo Z, Yau WM, Mattson MP, Tycko R (2005) Self-propagating, molecular-level polymorphism in Alzheimer’s beta-amyloid fibrils. Science 307:262–265PubMedCrossRefGoogle Scholar
  31. 31.
    Prusiner SB (1995) The prion diseases. Sci Am 272:48–51PubMedCrossRefGoogle Scholar
  32. 32.
    Prusiner SB (2001) Shattuck lecture—neurodegenerative diseases and prions. N Engl J Med 344:1516–1526PubMedCrossRefGoogle Scholar
  33. 33.
    Prusiner SB, Safar J, Cohen FE, DeArmond SJ (1999) The prion diseases. In: Terry RD, Katzman R, Bick KL, Sisodia SS (eds) Alzheimer disease. Lippincott Williams and Wilkins, Philadelphia, pp 161–179Google Scholar
  34. 34.
    Ritter C, Maddelein ML, Siemer AB, Luhrs T, Ernst M, Meier BH, Saupe SJ, Riek R (2005) Correlation of structural elements and infectivity of the HET-s prion. Nature 435:844–848PubMedCrossRefGoogle Scholar
  35. 35.
    Sigurdsson EM, Wisniewski T, Frangione B (2002) Infectivity of amyloid diseases. Trends Mol Med 8:411–413PubMedCrossRefGoogle Scholar
  36. 36.
    Silveira JR, Raymond GJ, Hughson AG, Race RE, Sim VL, Hayes SF, Caughey B (2005) The most infectious prion protein particles. Nature 437:257–261PubMedCrossRefGoogle Scholar
  37. 37.
    Tanaka M, Chien P, Yonekura K, Weissman JS (2005) Mechanism of cross-species prion transmission: an infectious conformation compatible with two highly divergent yeast prion proteins. Cell 121:49–62PubMedCrossRefGoogle Scholar
  38. 38.
    Unterberger U, Voigtlander T, Budka H (2005) Pathogenesis of prion diseases. Acta Neuropath 109:32–48PubMedCrossRefGoogle Scholar
  39. 39.
    Van Everbroeck B, Pals P, Martin JJ, Cras P (2002) Transmissible spongiform encephalopathies: the story of a pathogenic protein. Peptides 23:1351–1359PubMedCrossRefGoogle Scholar
  40. 40.
    Walker LC, LeVine H (2000) The cerebral proteopathies: neurodegenerative disorders of protein conformation and assembly. Mol Neurobiol 21:83–95PubMedCrossRefGoogle Scholar
  41. 41.
    Walker LC, LeVine H III (2002) Proteopathy: the next therapeutic frontier? Curr Opin Investig Drugs 3:782–787PubMedGoogle Scholar
  42. 42.
    Walker LC, LeVine H, Mattson MP, Jucker M (2006) Inducible proteopathies. TINS (in press)Google Scholar
  43. 43.
    Weissman C (2004) The state of the prion. Nat Rev Microbiol 2:861–871CrossRefGoogle Scholar
  44. 44.
    Weissmann C (2005) Birth of a prion: spontaneous generation revisited. Cell 122:165–168PubMedCrossRefGoogle Scholar
  45. 45.
    Xing Y, Nakamura A, Korenaga T, Guo Z, Yao J, Fu X, Matsushita T, Kogishi K, Hosokawa M, Kametani F, Mori M, Higuchi K (2002) Induction of protein conformational change in mouse senile amyloidosis. J Biol Chem 277:164–169CrossRefGoogle Scholar
  46. 46.
    Yamaguchi K, Takahashi S, Kawai T, Naiki H, Goto Y (2005) Seeding-dependent propagation and maturation of amyloid fibril conformation. J Mol Biol 352:952–960PubMedCrossRefGoogle Scholar
  47. 47.
    Zou WQ, Gambetti P (2005) From microbes to prions: the final proof of the prion hypothesis. Cell 121:155–157PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Yerkes National Primate Research Center and Department of Neurology Emory UniversityAtlantaUSA
  2. 2.Center on Aging, Department of Molecular and Cellular Biochemistry University of KentuckyLexingtonUSA
  3. 3.Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research University of TübingenTübingenGermany

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