The discovery of a new toxin in a strain of Enterococcus is raising scientific eyebrows. Isolated from cow feces sampled at a South Carolina farm, the bug was unexpectedly found to carry a toxin resembling the toxin that causes botulism. The finding was reported in the journal Cell Host and Microbe .
Min Dong said, "This is the first time a botulinum neurotoxin has been found outside of Clostridium botulinum and not just the toxin, but an entire unit containing the toxins and associated proteins that prevent the toxin from being degraded in the GI tract." The toxin, dubbed BoNT / En , is the ninth botulinum toxin to be described.
"The enterococcal isolate carrying the toxin luckily remains susceptible to key antibiotics," notes Jie Zhang. "It was found only once from a single animal, and no signs of botulism disease were observed."
When Sicai and his colleague tested the toxin in rodents in the lab, it had little or no effect. Only when they manipulated the toxin to better target mouse and mouse neurons did it become potent, shutting down nerve function and causing paralysis.
Researchers found that the BoNT / En botulinum toxin genes were carried by a plasmid. Plasmids are quite common in enterococci: in fact, they have been associated with the acquisition of resistance to vancomycin, a last-resort antibiotic, and transfer of resistance to the fearsome Staphylococcus aureus.
Gilmore's lab sequenced the toxin producing E. faecium strain as part of a much wider search for the origin of enterococcal antibiotic resistance and disease-causing ability. Lebreton co-first author had investigated the evolution of enterococci from its commensal Paleozoic origins its rise as a hospital threat.
Enter bioinformatician Andrew Doxey, specializes in mining genome data to discover new toxins and virulence genes. Analyzing the newly sequenced E. faecium genome, the lab's computer programs quickly spotted the genetic sequence for the novel botulinum toxin.
The newly discovered toxin does raise some concerns that botulinum toxin could turn up in antibiotic-resistant enterococci, perhaps stemming from the gene transfer in the gut of an animal harboring both C. botulinum and Enterococcus.
"This is a unique discovery of a botulinum neurotoxin in a bacterium that is both ubiquitous in animals and a serious problem in human health," said Lebreton. "
E. faecium is in the gut of nearly every human, it is extremely tough and survives a lot of stresses, often including efforts to disinfect hospital surfaces. A hospital-adapted, antibiotic-resistant, hard-to-kill bug carrying neurotoxin would be a worst-case scenario. "
Gilmore's lab continues to expand and study its collection of enterococcal isolates . "Most of what we know about Enterococcus comes from the few strains circulating in the hospital," said Lebreton. "It is possible that BoNT / En , or even other novel toxins, will turn up in other enterococci isolated from the wild." We just never looked for those before . "