This week, as contaminated cucumbers are being recalled across the United States due to a Salmonella outbreak that has killed two people and left more than 340 sick, scientists have announced a new strategy for combating foodborne disease. Their method involves genetically engineering plants to produce antimicrobial proteins, which can then be extracted and applied to contaminated meat and produce.
In a study published on Monday in the Proceedings of the National Academy of Sciences, the scientists engineered tobacco, leafy beets, spinach, chicory and lettuce to produce proteins called colicins, which can kill deadly strains of E. coli. The team, led by scientists from two German biotech companies, Nomad Bioscience and Icon Genetics, found that plants such as tobacco can yield high levels of active colicins. Furthermore, they identified a mixture of two colicins that can efficiently kill all major disease-causing strains of E. coli.
“All of the food outbreaks that have been recorded in the last 15 years or so could have been controlled very well by a combination of just two colicins, applied at very low concentrations,” said Yuri Gleba, CEO of Nomad Bioscience and one of the authors of the paper.
In the United States, nearly 300,000 E. coli infections occur each year, mainly through consumption of contaminated food. Most E. coli in food is found in contaminated beef and pork, but an increasing number of E. coli infections have been linked to organic produce, which is typically treated with animal manure in place of chemical fertilizers. According to the World Health Organization, up to 10 percent of E. coli infections could leading to life-threatening disease.
Colicins are proteins naturally produced by E. coli strains to kill or inhibit the growth of competing E. coli strains. The proteins are extremely toxic — so toxic, in fact, that engineering microbes to produce colicins usually ends up killing the hosts. To circumvent that problem, the study’s authors decided to engineer plants, since colicins are not as toxic to plant cells. They were successful at getting various plants to express large amounts of twelve different types of colicins — all of which were compositionally identical to colicins found naturally in E. coli.
“The yield that they’re getting through their plant source is much larger than what we would normally make in the lab with E. coli,” said William Cramer, a structural biologist who studies proteins at Purdue University.”
Colicins are extremely potent, which is why the scientists at Nomad and Icon believe the proteins could be an economically viable way to treat food. “Colicins are 50 times more active against bacteria than normal antibiotics,” said Gleba. In their study, Gleba and his colleagues sprayed E. coli-laced pork steaks with a mixture of two types of colicins, at 4 milligrams of colicin per kilogram of meat, and found significant reductions in E. coli after just an hour.
Their team also hired a third party to do an economic analysis of their process, and found that their method competes with the decontamination methods currently favored by the meat industry — namely heat processing and acid washes. “Normally the meat industry’s ready to spend two to five cents to treat one pound of meat,” said Gleba. “Our costs are lower than that.” Furthermore, Gleba believes their process is superior because, unlike heat and acid treatments, colicins don’t affect the quality and taste of the meat.
The team aims to get FDA approval of their process through a pathway called “generally recognized as safe,” or GRAS. Gleba said he is hopeful about the prospect, because colicins are naturally produced by E. coli in our intestines, and the small amount of colicins that they would use to treat food would be completely degraded in our stomach and digestive tract.
Other scientists, however, are not as immediately optimistic. Francisco Diez-Gonzalez, a food safety microbiologist at the University of Minnesota, warns that market approval could be a long, hard process. “To get approval for a food additive, you have to present a lot of toxicology studies and effectiveness studies,” he said. “I think it would be difficult to make the case that these colicins should qualify for GRAS, because they’re not typically part of the human diet.”
Still, Diez-Gonzalez admires the novelty of the scientists’ approach. “The feat of getting this protein to be expressed and produced at significant levels in plants is quite remarkable,” he said. “Just from a technological, scientific point of view, I think this study has a lot of merit.”
Other types of bacteria than E. coli can be killed with colicins, and Gleba and his team are planning to extend their process to these next. “We are already studying colicins for the control of Salmonella,” he told PopSci.