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Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium

Cell Host Microbe. 2018 Feb 14;23(2):169-176.e6. doi: 10.1016/j.chom.2017.12.018. Epub 2018 Jan 27.

Abstract

Botulinum neurotoxins (BoNTs), produced by various Clostridium strains, are a family of potent bacterial toxins and potential bioterrorism agents. Here we report that an Enterococcus faecium strain isolated from cow feces carries a BoNT-like toxin, designated BoNT/En. It cleaves both VAMP2 and SNAP-25, proteins that mediate synaptic vesicle exocytosis in neurons, at sites distinct from known BoNT cleavage sites on these two proteins. Comparative genomic analysis determines that the E. faecium strain carrying BoNT/En is a commensal type and that the BoNT/En gene is located within a typical BoNT gene cluster on a 206 kb putatively conjugative plasmid. Although the host species targeted by BoNT/En remains to be determined, these findings establish an extended member of BoNTs and demonstrate the capability of E. faecium, a commensal organism ubiquitous in humans and animals and a leading cause of hospital-acquired multi-drug-resistant (MDR) infections, to horizontally acquire, and possibly disseminate, a unique BoNT gene cluster.

Keywords: E. faecium; SNAP-25; SNARE; VAMP; botulinum neurotoxin; botulinum toxin; botulism; enterococcus; enterococcus faecium; toxin.

MeSH terms

  • Animals
  • Botulinum Toxins / genetics*
  • Botulinum Toxins / isolation & purification
  • Botulinum Toxins / toxicity*
  • Cattle
  • Cell Line
  • Enterococcus faecium / genetics*
  • Enterococcus faecium / pathogenicity*
  • Feces / microbiology
  • Female
  • Genome, Bacterial / genetics
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Multigene Family / genetics
  • Neurons / pathology
  • Plasmids / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Synaptosomal-Associated Protein 25 / metabolism*
  • Vesicle-Associated Membrane Protein 2 / metabolism*

Substances

  • Synaptosomal-Associated Protein 25
  • Vesicle-Associated Membrane Protein 2
  • Botulinum Toxins