Abstract
The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo.
Highlights
Basis of the use of Botulinum neurotoxins (BoNTs)/A1 and BoNT/B1 to treat many human syndromes characterized by hyperfunction of peripheral nerve terminals as the local injection of minute doses of the toxins reverts to a normal function[13,14,15,16]
The bioinformatics analysis of W. oryzae SG25T has led to the surprising identification of an open reading frame 1 that has a strong sequence similarity with bont genes, but lacks the additional genes usually associated within the bont locus in Clostridia[2,22]
The general and relevant conclusion of the present work is that the putative BoNT-like LC encoded by Weissella oryzae SG25T is a metalloprotease similar to the Clostridial botulinum neurotoxins
Summary
Basis of the use of BoNT/A1 and BoNT/B1 to treat many human syndromes characterized by hyperfunction of peripheral nerve terminals as the local injection of minute doses of the toxins reverts to a normal function[13,14,15,16]. Very recently the complete genome of Weissella oryzae SG25T, a facultative anaerobe isolated from fermenting rice, an ecological niche that is shared by anaerobic Clostridia, has been determined[18]. Members of the genus Weissella are widely distributed in meat, fermented vegetables and soil. The bioinformatics analysis of W. oryzae SG25T has led to the surprising identification of an open reading frame 1 (orf1) that has a strong sequence similarity with bont genes, but lacks the additional genes usually associated within the bont locus in Clostridia[2,22]
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