Peroxymonosulfate Rapidly Inactivates the Disease-Associated Prion Protein

Abstract

Prions, the etiological agents in transmissible spongiform encephalopathies, exhibit remarkable resistance to most methods of inactivation that are effective against conventional pathogens. Prions are composed of pathogenic conformers of the prion protein (PrPTSE). Some prion diseases are transmitted, in part, through environmental routes. The recalcitrance of prions to inactivation may lead to a persistent reservoir of infectivity that contributes to the environmental maintenance of epizootics. At present, few methods exist to remediate prion-contaminated lands. Here we examined the ability of peroxymonosulfate to degrade PrPTSE as an initial step toward developing an in situ chemical oxidation process to inactivate prions. We find that peroxymonosulfate rapidly degrades PrPTSE from two species. Transition metal-catalyzed decomposition of peroxymonosulfate to produce sulfate radicals appears to enhance degradation. We further demonstrate that exposure to peroxymonosulfate significantly reduced PrPC-to-PrPTSE converting ability as measured by protein misfolding cyclic amplification, used as a proxy for infectivity. Liquid chromatography-tandem mass spectrometry revealed that exposure to peroxymonosulfate results in oxidative modifications to methionine and tryptophan residues. This study indicates that peroxymonosulfate may hold promise for in situ remediation of prion-contaminated surfaces.

Peroxymonosulfate Oxidizes Amino Acids in Water without Activation

“…The MetO product could be further oxidized by PMS to produce MetO 2 . Oxidation of the pathogenic prion protein by PMS in the absence of transition metal activation has also been shown to result in the oxidation of Met to MetO 2 …”

“…For example, PMS reacts with phenol to form benzene-1,4-diol . Oxidation of the pathogenic prion protein by HSO 5 – in the absence of transition metal activation has also been shown to result in the oxidation of Trp to OH-Trp . Several additional Trp oxidation products were present in the reaction mixtures.…”

“…These limitations have prompted the investigation of peroxymonosulfate (PMS) as an alternate bulk oxidant in ISCO and advanced oxidation processes . We previously demonstrated that PMS can rapidly inactivate prions and degrade pathogenic prion protein …”

Activation of persulfates by natural magnetic pyrrhotite for water disinfection: Efficiency, mechanisms, and stability

“…In recent decades, sulfate radicals (•SO 4 − ) based advanced oxidation process (AOP) has attracted increasing interests in water treatment, due to their high efficiency in degrading a wide range of recalcitrant micro-contaminants (Drzewicz et al, 2012;Yuan et al, 2014) and even inactivating biohazards (Anipsitakis et al, 2008;Tsitonaki et al, 2008;Chesney et al, 2016). For instance, Michael-Kordatou et al (2015a) evidence that the UVC/PS process can result in rapid and complete erythromycin (ERY) degradation and ERY-resistant Escherichia coli inactivation in secondary treated wastewater, thus to produce a final treated effluent with lower phytotoxicity (<10%) compared to the untreated wastewater. )…”

Kinetics of Oxidation of Iodide (I–) and Hypoiodous Acid (HOI) by Peroxymonosulfate (PMS) and Formation of Iodinated Products in the PMS/I–/NOM System

“…Yang et al 19 found that PMS could effectively remove sulfur-containing odor compound mercaptan in a wet scrubbing process. Very recently, Chesney and co-workers 26 demonstrated that PMS could rapidly inactivate the disease-associated pathogenic prion protein in contaminated land surfaces by an oxidative modification to the amino acid residuals of the peptide fragments. However, there is only limited information about halogen transformation during PMS oxidation and/or disinfection.…”