Harnessing Prions As Test Agents for the Development of Broad-range Disinfectants

Overview

Journal Prion

Specialty Biochemistry

Date 2012 Mar 29

PMID 22453169

Authors

Katja Wagenfuhr

Michael Beekes

Affiliations

Soon will be listed here.

Abstract

The development of disinfectants with broad-range efficacy against bacteria, viruses, fungi, protozoa and prions constitutes an ongoing challenge. Prions, the causative agents of transmissible spongiform encephalopathies (TSEs) such as Creutzfeldt-Jakob disease (CJD) or its variant (vCJD) rank among the pathogens with the highest resistance to disinfection. Pilot studies have shown that procedures devised for prion disinfection were also highly effective against microbial pathogens. This fueled the idea to systematically exploit prions as test pathogens for the identification of new potential broad-range disinfectants. Prions essentially consist of misfolded, aggregated prion protein (PrP) and putatively replicate by nucleation-dependent, or seeded PrP polymerization. Recently, we have been able to establish PrP seeding activity as a quantitative in vitro indicator for the disinfection of 263K scrapie prions on steel wires used as surrogates for medical instruments. The seeding activity on wires re-processed in different disinfectants could be (1) biochemically determined by quantitative protein misfolding cyclic amplification (qPMCA), (2) biologically detected after qPMCA in a cell assay and (3) correctly translated into residual titres of scrapie infectivity. Our approach will substantially facilitate the identification of disinfectants with efficacy against prions as promising candidates for a further microbiological validation of broad-range activity.

References

Lehmann S, Pastore M, Rogez-Kreuz C, Richard M, Belondrade M, Rauwel G . New hospital disinfection processes for both conventional and prion infectious agents compatible with thermosensitive medical equipment. J Hosp Infect. 2009; 72(4):342-50. DOI: 10.1016/j.jhin.2009.03.024. View

Peretz D, Supattapone S, Giles K, Vergara J, Freyman Y, Lessard P . Inactivation of prions by acidic sodium dodecyl sulfate. J Virol. 2005; 80(1):322-31. PMC: 1317507. DOI: 10.1128/JVI.80.1.322-331.2006. View

Gonzalez-Montalban N, Makarava N, Ostapchenko V, Savtchenk R, Alexeeva I, Rohwer R . Highly efficient protein misfolding cyclic amplification. PLoS Pathog. 2011; 7(2):e1001277. PMC: 3037363. DOI: 10.1371/journal.ppat.1001277. View

McDonnell G, Burke P . Disinfection: is it time to reconsider Spaulding?. J Hosp Infect. 2011; 78(3):163-70. DOI: 10.1016/j.jhin.2011.05.002. View

Chen B, Morales R, Barria M, Soto C . Estimating prion concentration in fluids and tissues by quantitative PMCA. Nat Methods. 2010; 7(7):519-20. PMC: 4049222. DOI: 10.1038/nmeth.1465. View

Klohn P, Stoltze L, Flechsig E, Enari M, Weissmann C . A quantitative, highly sensitive cell-based infectivity assay for mouse scrapie prions. Proc Natl Acad Sci U S A. 2003; 100(20):11666-71. PMC: 208815. DOI: 10.1073/pnas.1834432100. View

Bieschke J, Weber P, Sarafoff N, Beekes M, Giese A, Kretzschmar H . Autocatalytic self-propagation of misfolded prion protein. Proc Natl Acad Sci U S A. 2004; 101(33):12207-11. PMC: 514458. DOI: 10.1073/pnas.0404650101. View

Collins S, Law M, Fletcher A, Boyd A, Kaldor J, Masters C . Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study. Lancet. 1999; 353(9154):693-7. DOI: 10.1016/s0140-6736(98)08138-0. View

Caughey B, Baron G, Chesebro B, Jeffrey M . Getting a grip on prions: oligomers, amyloids, and pathological membrane interactions. Annu Rev Biochem. 2009; 78:177-204. PMC: 2794486. DOI: 10.1146/annurev.biochem.78.082907.145410. View

10.

Beekes M, Lemmer K, Thomzig A, Joncic M, Tintelnot K, Mielke M . Fast, broad-range disinfection of bacteria, fungi, viruses and prions. J Gen Virol. 2009; 91(Pt 2):580-9. DOI: 10.1099/vir.0.016337-0. View

11.

Brown P, Rohwer R, Gajdusek D . Newer data on the inactivation of scrapie virus or Creutzfeldt-Jakob disease virus in brain tissue. J Infect Dis. 1986; 153(6):1145-8. DOI: 10.1093/infdis/153.6.1145. View

12.

Eisele Y, Obermuller U, Heilbronner G, Baumann F, Kaeser S, Wolburg H . Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science. 2010; 330(6006):980-2. PMC: 3233904. DOI: 10.1126/science.1194516. View

13.

Wilham J, Orru C, Bessen R, Atarashi R, Sano K, Race B . Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS Pathog. 2010; 6(12):e1001217. PMC: 2996325. DOI: 10.1371/journal.ppat.1001217. View

14.

Edgeworth J, Jackson G, Clarke A, Weissmann C, Collinge J . Highly sensitive, quantitative cell-based assay for prions adsorbed to solid surfaces. Proc Natl Acad Sci U S A. 2009; 106(9):3479-83. PMC: 2637901. DOI: 10.1073/pnas.0813342106. View

15.

Brown P, Gibbs Jr C, Rodgers-Johnson P, Asher D, Sulima M, Bacote A . Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol. 1994; 35(5):513-29. DOI: 10.1002/ana.410350504. View

16.

Murayama Y, Yoshioka M, Horii H, Takata M, Yokoyama T, Sudo T . Protein misfolding cyclic amplification as a rapid test for assessment of prion inactivation. Biochem Biophys Res Commun. 2006; 348(2):758-62. DOI: 10.1016/j.bbrc.2006.07.130. View

17.

Weber P, Giese A, Piening N, Mitteregger G, Thomzig A, Beekes M . Cell-free formation of misfolded prion protein with authentic prion infectivity. Proc Natl Acad Sci U S A. 2006; 103(43):15818-23. PMC: 1635086. DOI: 10.1073/pnas.0605608103. View

18.

Brown P, Cervenakova L . A prion lexicon (out of control). Lancet. 2005; 365(9454):122. DOI: 10.1016/S0140-6736(05)17700-9. View

19.

Saborio G, Permanne B, Soto C . Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature. 2001; 411(6839):810-3. DOI: 10.1038/35081095. View

20.

Giles K, Glidden D, Beckwith R, Seoanes R, Peretz D, DeArmond S . Resistance of bovine spongiform encephalopathy (BSE) prions to inactivation. PLoS Pathog. 2008; 4(11):e1000206. PMC: 2576443. DOI: 10.1371/journal.ppat.1000206. View