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Open AccessArticle

Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland
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Author to whom correspondence should be addressed.
Toxins 2020, 12(1), 19; https://doi.org/10.3390/toxins12010019
Received: 9 December 2019 / Revised: 23 December 2019 / Accepted: 29 December 2019 / Published: 31 December 2019
(This article belongs to the Special Issue Clostridium Neurotoxins)
The botulinum neurotoxin (BoNT) has been extensively researched over the years in regard to its structure, mode of action, and applications. Nevertheless, the biological roles of four proteins encoded from a number of BoNT gene clusters, i.e., OrfX1-3 and P47, are unknown. Here, we investigated the diversity of orfX-p47 gene clusters using in silico analytical tools. We show that the orfX-p47 cluster was not only present in the genomes of BoNT-producing bacteria but also in a substantially wider range of bacterial species across the bacterial phylogenetic tree. Remarkably, the orfX-p47 cluster was consistently located in proximity to genes coding for various toxins, suggesting that OrfX1-3 and P47 may have a conserved function related to toxinogenesis and/or pathogenesis, regardless of the toxin produced by the bacterium. Our work also led to the identification of a putative novel BoNT-like toxin gene cluster in a Bacillus isolate. This gene cluster shares striking similarities to the BoNT cluster, encoding a bont/ntnh-like gene and orfX-p47, but also differs from it markedly, displaying additional genes putatively encoding the components of a polymorphic ABC toxin complex. These findings provide novel insights into the biological roles of OrfX1, OrfX2, OrfX3, and P47 in toxinogenesis and pathogenesis of BoNT-producing and non-producing bacteria.
Keywords: botulinum neurotoxin; neurotoxin gene cluster; orfX; p47; neurotoxin associated proteins botulinum neurotoxin; neurotoxin gene cluster; orfX; p47; neurotoxin associated proteins
MDPI and ACS Style

Nowakowska, M.B.; Douillard, F.P.; Lindström, M. Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species. Toxins 2020, 12, 19.

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