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. Botulinum neurotoxins (BoNTs) are potent toxins produced by diverse bacteria in the Clostridium genus. Zhang et al. report that a commensal strain of Enterococcus faecium carries a conjugative plasmid encoding a BoNT-like toxin gene. Thus, a commensal organism can acquire and possibly disseminate BoNT genes.
| Original language | English |
|---|---|
| Pages (from-to) | 169-176.e6 |
| Journal | Cell Host and Microbe |
| Volume | 23 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 14 Feb 2018 |
Funding
We thank Edwin R. Chapman (Univ. of Wisconsin, Madison), Shashi Sharma (FDA), Chuan Hu (Univ. of Louisville), Bradley L. Pentelute (MIT), and Jesse C. Hay (University of Montana) for providing antibodies, cDNA, and other critical reagents; Daria Van Tyne and Katarina Schaufler for the collection of enterococcal isolates; Anthony Gaca for MinION sequencing; Ashlee Earl for bioinformatic analyses; and Linda Henriksson for assisting the production of BoNT/X polyclonal antibody. This study was partially supported by National Institute of Health (NIH) grants ( NS080833 and AI132387 ) to M.D.; NIH/NIAID grants ( AI072360 , AI108710 , and the Harvard-wide Antibiotic Resistance Program, AI083214 ) to M.S.G.; and the Swedish Research Council ( 2014-5667 ), the Wenner-Gren Foundation , and the Swedish Cancer Society (to P.S.). J.A.S. was supported by a fellowship from NIH ( F32GM121005 ). A.C.D. acknowledges funding from the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant RGPIN-435973-2013) and an Ontario Early Researcher Award . M.D. also acknowledges support by the NIH-funded Harvard Digestive Disease Center ( P30DK034854 ), Boston Children’s Hospital Intellectual and Developmental Disabilities Research Center ( P30HD18655 ), and the FunGCAT program from the Office of the Director of National Intelligence (ODNI) , Intelligence Advanced Research Projects Activity (IARPA) , via the Army Research Office (ARO) under Federal Award No. W911NF-17-2-0089 . The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the ODNI, IARPA, ARO, or the US Government. M.D. holds the Investigator in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund .
Keywords
- botulinum neurotoxin
- botulinum toxin
- botulism
- E. faecium
- enterococcus
- enterococcus faecium
- SNAP-25
- SNARE
- toxin
- VAMP
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Virology