Studies on botulinum neurotoxins type /C1 and mosaic/DC using Endopep-MS and proteomics

FEMS Immunol Med Microbiol. 2011 Apr;61(3):288-300. doi: 10.1111/j.1574-695X.2010.00774.x. Epub 2011 Jan 26.

Abstract

Botulinum neurotoxins (BoNTs) are very potent toxins and category A biological threat agents. BoNT serotypes /C1 and /D affect birds and mammals and can be potentially lethal to humans. We have previously described the usefulness of the Endopep-MS method to detect the activity of BoNT A through G. This report was followed by the application of the method to clinical samples. The activity of the BoNT serotypes associated with human disease (/A, /B, /E, and /F) was successfully detected. However, BoNT/C and /D require different conditions for fast substrate cleavage, and a comprehensive description of a method to study BoNT/C and /D has not yet been reported. This work describes a new, optimized version of the Endopep-MS method to detect BoNTs /C1 and /DC either spiked directly in 20 μL of reaction buffer or spiked in a larger volume of buffer and further extracted using antibody-coated magnetic beads. It was found that the incubation temperature at 42 °C was more effective for both toxin serotypes, but each toxin serotype has an optimum cleavage pH. Additionally, we describe for the first time a proteomics study using a fast trypsin digestion method and label-free quantification of these toxin serotypes.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Botulinum Toxins / analysis*
  • Endopeptidases / analysis
  • Humans
  • Mass Spectrometry / methods
  • Toxicology / methods*

Substances

  • botulinum toxin type D
  • Endopeptidases
  • Botulinum Toxins
  • botulinum toxin type C