De novo subtype and strain identification of botulinum neurotoxin type B through toxin proteomics

Kalb, Suzanne R.; Baudys, Jakub; Rees, Jon C.; Smith, Theresa J.; Smith, Leonard A.; Helma, Charles H.; Hill, Karen; Kull, Skadi; Kirchner, Sebastian; Dorner, Martin B.; Dorner, Brigitte G.; Pirkle, James L.; Barr, John R.

doi:10.1007/s00216-012-5767-3

De novo subtype and strain identification of botulinum neurotoxin type B through toxin proteomics

Journal Article · Tue Mar 06 23:00:00 EST 2012 · Analytical and Bioanalytical Chemistry

DOI:https://doi.org/10.1007/s00216-012-5767-3· OSTI ID:1815820

Kalb, Suzanne R. ^[1]; Baudys, Jakub ^[2]; Rees, Jon C. ^[2]; Smith, Theresa J. ^[3]; Smith, Leonard A. ^[4]; Helma, Charles H. ^[5]; Hill, Karen ^[5]; Kull, Skadi ^[6]; Kirchner, Sebastian ^[6]; Dorner, Martin B. ^[6]; Dorner, Brigitte G. ^[6]; Pirkle, James L. ^[2]; Barr, John R. ^[2]

Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States). National Center for Environmental Health. Division of Lab. Sciences; OSTI
Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States). National Center for Environmental Health. Division of Lab. Sciences
US Army Medical Research Inst. of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States). Integrated Toxicology
Medical Research and Materiel Command (MRMC), Fort Detrick, MD (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division
Robert Koch-Institut, Berlin (Germany). Center for Biological Security. Microbial Toxins (ZBS3)

Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. There are seven known serotypes of BoNT, A–G, defined by their response to antisera. Many serotypes are distinguished into differing subtypes based on amino acid sequence, and many subtypes are further differentiated into toxin variants. Previous work in our laboratory described the use of a proteomics approach to distinguish subtype BoNT/A1 from BoNT/A2 where BoNT identities were confirmed after searching data against a database containing protein sequences of all known BoNT/A subtypes. We now describe here a similar approach to differentiate subtypes BoNT/B1, /B2, /B3, /B4, and /B5. Additionally, to identify new subtypes or hitherto unpublished amino acid substitutions, we created an amino acid substitution database covering every possible amino acid change. We used this database to differentiate multiple toxin variants within subtypes of BoNT/B1 and B2. More importantly, with our amino acid substitution database, we were able to identify a novel BoNT/B subtype, designated here as BoNT/B7. These techniques allow for subtype and strain level identification of both known and unknown BoNT/B rapidly with no DNA required.

View Accepted Manuscript (DOE)

Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1815820

Journal Information:: Analytical and Bioanalytical Chemistry, Journal Name: Analytical and Bioanalytical Chemistry Journal Issue: 1 Vol. 403; ISSN 1618-2642

Publisher:: SpringerCopyright Statement

Country of Publication:: United States

Language:: English

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