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bioRxiv · 10.1101/2025.01.16.633459

Identification of a divergent botulinum neurotoxin like gene cluster in Furfurilactobacillus

Wei, X.·Lee, P.-G.·Dong, M.·Doxey, A. C.
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Abstract

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins and are traditionally associated with Clostridium species. However, recent discoveries have identified BoNT-like proteins in diverse bacterial genera, revealing an expanding family of neurotoxins with unique evolutionary and functional traits. In this study, we report the identification of a novel BoNT-like gene cluster in Furfurilactobacillus sp. OKN36, encoding a toxin we tentatively designate as "Furfuritoxin". Sequence and structural analyses indicate that Furfuritoxin shares key domains with clostridial neurotoxins, including a light chain zinc metalloprotease domain and heavy chain translocase and binding domains, while exhibiting significant sequence divergence. Phylogenetic analysis places Furfuritoxin within a divergent lineage alongside previously reported BoNT/Wo, suggesting a shared ancestral relationship. Gene neighborhood analysis reveals features shared with other BoNT gene clusters including ORFX-related genes and conjugation-associated elements, indicating horizontal gene transfer may have facilitated its distribution. This study adds to the growing family of BoNT-like toxins, providing insights into their evolution and diversity.

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Wei, X., Lee, P.-G., Dong, M., Doxey, A. C.. 2025-01-21. Identification of a divergent botulinum neurotoxin like gene cluster in Furfurilactobacillus. https://doi.org/10.1101/2025.01.16.633459

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