Proteomic Methods of Detection and Quantification of Protein Toxins

Abstract

Biological toxins are a heterogeneous group of compounds that share commonalities with biological and chemical agents. Among them, protein toxins represent a considerable, diverse set. They cover a broad range of molecular weights from less than 1000 Da to more than 150 kDa. This review aims to compare conventional detection methods of protein toxins such as in vitro bioassays with proteomic methods, including immunoassays and mass spectrometry-based techniques and their combination. Special emphasis is given to toxins falling into a group of selected agents, according to the Centers for Disease Control and Prevention, such as Staphylococcal enterotoxins, Bacillus anthracis toxins, Clostridium botulinum toxins, Clostridium perfringens epsilon toxin, ricin from Ricinus communis, Abrin from Abrus precatorius or control of trade in dual-use items in the European Union, including lesser known protein toxins such as Viscumin from Viscum album. The analysis of protein toxins and monitoring for biological threats, i.e., the deliberate spread of infectious microorganisms or toxins through water, food, or the air, requires rapid and reliable methods for the early identification of these agents.

Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

“…It is hereby of great importance to distinguish between functionally active vs. denatured ricin, since this has important implications on emergency operating schedules, therapeutic measures, and forensic analysis. This relies on performing functional assays, which also allow for the differentiation between A-chain vs. B-chain activity, or both (see Duracova et al 2018).…”

“…Consequently, considerable research efforts have been focused on the development of sensitive methods for the detection of ricin D in complex matrices such as human biological samples, environmental samples, water, and food (Kalb and Barr 2009;Severino et al 2012;Worbs et al 2015;Stern et al 2018;Weber 2018). Possibilities of ricin detection are the lateral flow assay (LFA), the detection of ricinin as accompanying alkaloid in castor bean seeds, polymerase chain reaction (PCR)-based detection of DNA (only applicable in castor bean seeds), or liquid chromatography/mass spectrometry (LC/MS) after protein digestion (Weber and Schulz 2011;Worbs et al 2015;Duracova et al 2018;Weber 2018). Furthermore, a variety of immunological methods for ricin detection exist, whereby enzyme-linked immunosorbent assays (ELISA) has been proven to be one of the most versatile techniques (for review, see Severino et al 2012).…”

Towards Protecting Critical National Assets and Preparedness for Response to Hazardous Chemical, Biological and Radiological Attacks

“…Delayed acting chemical agents and bio-toxins, e.g., mustard, arsine, botulinum toxin, ricin etc., toxic chemicals that cause no or very few detectable symptoms, may take from hours to days to show effects. Contagious and non-contagious biological agents biological agents causes no initial symptoms, or typically flu-like symptoms after a few days or weeks, and are problematic after the victims become symptomatic 25 .…”

Highly Toxic Ribosome-Inactivating Proteins As chemical Warfare or Terrorist Agents

“…This interruption induces a cellular stress response, which triggers the release of cytokines by the target cell and, at high viscumin concentrations, apoptosis of the cell (Thies et al, 2005). Viscumin belongs to a group of selected substances, according to the Centers for Disease Control and Prevention, or the control of trade in dual-use products in the European Union (Duracova et al, 2018).…”