Advanced

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

Zhang, Sicai; Lebreton, Francois; Mansfield, Michael J; Miyashita, Shin-Ichiro; Zhang, Jie; Schwartzman, Julia A; Tao, Liang; Masuyer, Geoffrey; Martínez-Carranza, Markel and Stenmark, Pål LU , et al. (2018) In Cell Host and Microbe 23(2). p.6-176
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
@article{fdc62c17-79e1-48ef-8ceb-d1351a520afd,
  abstract     = {<p>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.</p>},
  author       = {Zhang, Sicai and Lebreton, Francois and Mansfield, Michael J and Miyashita, Shin-Ichiro and Zhang, Jie and Schwartzman, Julia A and Tao, Liang and Masuyer, Geoffrey and Martínez-Carranza, Markel and Stenmark, Pål and Gilmore, Michael S and Doxey, Andrew C and Dong, Min},
  issn         = {1934-6069},
  keyword      = {Animals,Botulinum Toxins/genetics,Cattle,Cell Line,Enterococcus faecium/genetics,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},
  language     = {eng},
  month        = {02},
  number       = {2},
  pages        = {6--176},
  publisher    = {Elsevier},
  series       = {Cell Host and Microbe},
  title        = {Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium},
  url          = {http://dx.doi.org/10.1016/j.chom.2017.12.018},
  volume       = {23},
  year         = {2018},
}