Surprise: Botulinum-type toxins jump to other bacteria
Staff Writer |
Enterococci are hardy microbes that thrive in the gastrointestinal tracts of nearly all land animals, including our own, and generally cause no harm.
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But their ruggedness has lately made them leading causes of multi-drug-resistant infections, especially in settings like hospitals where antibiotic use disrupts the natural balance of intestinal microbes.
So 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 January 25 in the journal Cell Host and Microbe.
"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 toxin and associated proteins that prevent the toxin from being degraded in the GI tract," says Min Dong, PhD, a scientist in Boston Children's Hospital's Department of Urology and Harvard Medical School and one of the world's experts on botulinum toxins.
The toxin, dubbed BoNT/En, is the ninth botulinum toxin to be described. (Last August, Dong and colleagues reported the eighth, BoNT/X, made by C. botulinum and the first new botulinum toxin to be found in close to 50 years.
No, at least not yet, says Sicai Zhang, PhD, a postdoctoral fellow in Dong's lab and one of three co-first authors authors on the new report.
"The enterococcal isolate carrying the toxin luckily remains susceptible to key antibiotics," notes Zhang. "It was found only once from a single animal, and no signs of botulism disease were observed."
When Sicai and his colleague Jie Zhang, PhD, 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 rat neurons did it become potent, shutting down nerve function and causing paralysis.
Is BoNT/En toxic to humans? Dong's lab is now testing it in cultured human neurons to find out.
How could this botulinum toxin jump from one bacterial species to another? Teams led by Dong's collaborators, Michael Gilmore, PhD, at Massachusetts Eye and Ear and Harvard Medical School, and Andrew Doxey, PhD, at the University of Waterloo, found that the BoNT/En botulinum toxin genes were carried by a plasmid.
Plasmids are mobile structures that contain DNA independently of the chromosomes, and can be swapped from one bacterium to another.
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.
This ability to swap genes is what worries scientists. Could a potent toxin from C. botulinum end up in a multi-drug-resistant E. faecium strain? It now seems theoretically possible.
"Enterococcus is a central hub for gene transfer within the gut, and that makes it potentially scary," says Dong.
Gilmore's lab sequenced the toxin producing E. faecium strain as part of a much wider search for the origins of enterococcal antibiotic resistance and disease-causing ability.
"We were not looking for a neurotoxin in E. faecium," says Francois Lebreton, PhD, another co-first author on the paper who specializes in examining the genome sequences of these microbes. "There was no reason to suspect its existence."
Lebreton has been investigating the evolution of enterococci from its commensal Paleozoic origins its rise as a hospital threat. ■