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

Maria B. Nowakowska, Francois P. Douillard, Miia Lindström

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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.
Original languageEnglish
Article number19
JournalToxins
Volume12
Issue number1
Number of pages19
ISSN2072-6651
DOIs
Publication statusPublished - 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 416 Food Science
  • 1183 Plant biology, microbiology, virology
  • botulinum neurotoxin
  • neurotoxin gene cluster
  • orfX
  • p47
  • neurotoxin associated proteins
  • BOTULINUM NEUROTOXIN GENE
  • MULTIPLE SEQUENCE ALIGNMENT
  • C PROGENITOR TOXIN
  • PROTEIN-STRUCTURE
  • SWISS-MODEL
  • MOLECULAR CHARACTERIZATION
  • NUCLEOTIDE-SEQUENCE
  • EPITHELIAL-CELLS
  • DOMAIN
  • PHOTORHABDUS
  • 1182 Biochemistry, cell and molecular biology

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