title: Mass spectrometric detection of protein-based toxins.
abstract: This review focuses on mass spectrometric detection of protein-based toxins, which are among the most toxic substances known. Special emphasis is given to the bacterial toxins botulinum neurotoxin from Clostridium botulinum and anthrax toxins from Bacillus anthracis as well as the plant toxin ricin produced by Ricinus communis. A common feature, apart from their extreme toxicity, is that they are composed of 2 polypeptide chains, one of which is responsible for cell uptake and another that has enzymatic function with the ability to destroy basic cellular functions. These toxins pose a threat, both regarding natural spread and from a terrorism perspective. In order for public health and emergency response officials to take appropriate action in case of an outbreak, whether natural or intentional, there is a need for fast and reliable detection methods. Traditionally, large molecules like proteins have been detected using immunological techniques. Although sensitive, these methods suffer from some drawbacks, such as the risk of false-positives due to cross-reactions and detection of inactive toxin. This article describes recently developed instrumental methods based on mass spectrometry for the reliable detection of botulinum neurotoxins, anthrax toxins, and ricin. Unequivocal identification of a protein toxin can be carried out by mass spectrometry-based amino acid sequencing. Furthermore, in combination with antibody affinity preconcentration and biochemical tests with mass spectrometric detection demonstrating the toxin's enzymatic activity, very powerful analytical methods have been described. In conclusion, the advent of sensitive, easily operated mass spectrometers provides new possibilities for the detection of protein-based toxins.
authors: Annica Tevell Åberg, PhD, is a Senior Researcher; Kristian Björnstad, PhD, is a Senior Researcher; and Mikael Hedeland, PhD, is an Associate Professor and Deputy Head of Department; all at the Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA) , Uppsala, Sweden. Dr. Åberg and Dr. Hedeland are also affiliated with the Division of Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden .
authors: Annica
authors: A
authors: Tevell Åberg
authors: Kristian
authors: K
authors: Björnstad
authors: Mikael
authors: M
authors: Hedeland
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry*; D001427:Bacterial Toxins / Q000737:chemistry*; D001905:Botulinum Toxins / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D012276:Ricin / Q000737:chemistry*; D020539:Sequence Analysis, Protein
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D012276:Ricin; D001905:Botulinum Toxins