Abstract
Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs), toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC), alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs) to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH), and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC), but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs) which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.
Highlights
Botulinum neurotoxins (BoNTs) are toxic proteins created by Clostridium botulinum and some related clostridia
We studied progenitor toxin complexes of 14 from three bivalent C. botulinum strains; BoNT/A1(B), BoNT/A2b, and /A2f, which each3contain at least one toxin gene cluster in combination with either a HA+
This the bivalent makes two active toxins. Toxin from this culture role toxin of thestrain classic neurotoxin-associated proteins (NAPs) is notsupernatant completely was extracted with antibodies to
Summary
Botulinum neurotoxins (BoNTs) are toxic proteins created by Clostridium botulinum and some related clostridia. The minimally functional PTC (M-PTC) of all serotypes and subtypes contains the neurotoxin and a protein of similar molecular weight known as the non-toxic non-hemagglutinin (NTNH) protein. In 2005, a mass spectrometric characterization of botulinum progenitor toxins reported that the BoNT/E3 complex contains a protein encoded by orfX1 [14]. A more recent study from 2010 reports that the PTC of BoNT/A2 contains proteins encoded by both orfX2 and orfX3, but that these proteins are not present in the purified toxin complex, which consists only of. Our laboratory decided to utilize our experience in proteomic analyses of botulinum neurotoxins to examine the protein composition of several hemagglutinin negative botulinum progenitor toxin complexes. We studied progenitor toxin complexes of 14 from three bivalent C. botulinum strains; BoNT/A1(B), BoNT/A2b, and /A2f, which each3contain at least one toxin gene cluster in combination with either a HA+. Existence of the proteins encoded by orfX1, orfX2, and/or orfX3 in many orfX+ progenitor toxin complexes that we studied
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