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bioRxiv · 10.1101/2022.08.17.504336

Identification of divergent botulinum neurotoxin homologs in Paeniclostridium ghonii

Wei, X.·Wentz, T.·Lobb, B.·Mansfield, M. J.·Zhen, W.·Tan, H.·Wu, Z.·Pellett, S.·Dong, M.·Doxey, A. C.
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Abstract

Botulinum neurotoxins (BoNTs) are the most potent family of toxins known to science. Bioinformatic studies in recent years have revealed that they are members of a broader toxin family, with an increasing number of divergent homologs identified in genomes of organisms outside of the Clostridium genus. Here, we report the identification of two putative divergent BoNT-like homologs in the genomes of two strains of Paeniclostridium ghonii. We designated them PG-toxin 1 (PGT1) and PG-toxin 2 (PGT2), which share ~54% protein sequence identity. Unlike any other known BoNT homologs, PGT1 and PGT2 are composed of two separate subunits encoded on two neighboring genes: one encoding the protease domain (light chain, LC) with a conserved HExxH motif, and the second encoding the heavy-chain (HC) containing the putative translocation domain and receptor-binding domain. Phylogenetic analysis of both the LC and HC reveal that it is a divergent member of the lineage of BoNT that also includes BoNT/X, BoNT/En and the insecticidal PMP1. The gene clusters harboring PGT1 and PGT2 also include a putative insecticidal delta-endotoxin, Cry8Ea1, as well as putative endolysin and bacteriocin genes that may facilitate lytic toxin secretion, suggesting a possibility that this gene cluster might serve an insecticidal purpose.

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Wei, X., Wentz, T., Lobb, B., Mansfield, M. J., Zhen, W., Tan, H., Wu, Z., Pellett, S., Dong, M., Doxey, A. C.. 2022-08-18. Identification of divergent botulinum neurotoxin homologs in Paeniclostridium ghonii. https://doi.org/10.1101/2022.08.17.504336

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