title: De novo subtype and strain identification of botulinum neurotoxin type B through toxin proteomics.
abstract: 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 Additionally, to identify new subtypes or hitherto unpublished amino acid substitutions, we created an amino acid substitution database covering every possible amino acid change.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.
authors.affiliation: Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Atlanta, GA 30341, USA.
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Kalb
authors.forename: Jakub
authors.initials: J
authors.lastname: Baudys
authors.forename: Jon C
authors.initials: JC
authors.lastname: Rees
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Smith
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Smith
authors.forename: Charles H
authors.initials: CH
authors.lastname: Helma
authors.forename: Karen
authors.initials: K
authors.lastname: Hill
authors.forename: Skadi
authors.initials: S
authors.lastname: Kull
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kirchner
authors.forename: Martin B
authors.initials: MB
authors.lastname: Dorner
authors.forename: Brigitte G
authors.initials: BG
authors.lastname: Dorner
authors.forename: James L
authors.initials: JL
authors.lastname: Pirkle
authors.forename: John R
authors.initials: JR
authors.lastname: Barr
mesh_terms: D000595:Amino Acid Sequence; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism*; D019274:Botulinum Toxins, Type A; D008969:Molecular Sequence Data; D040901:Proteomics; D053719:Tandem Mass Spectrometry
chemical_list: C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A