In terms of deaths-per-infection, this year’s Listeria outbreak in cantaloupes ranks as the deadliest foodborne illness outbreak in U.S. history, killing 31 of the 146 people infected and causing one miscarriage. A new discovery by a team of researchers at Cornell University, however, could eventually lead to therapeutic solutions that the team hopes would treat Listeria infections and fight deadly outbreaks.
In a study published by microbiology journal mBio on November 29, the Cornell team has identified a small antibiotic compound that stops Listeria from using the defense mechanisms that allow it to survive stomach acids and the other perils of human digestion and food processing.
“This is probably the most exciting discovery of my career,” said Kathryn J. Boor, Ph.D., dean of agriculture and life sciences at Cornell and co-author of the study.
With access to the library of compounds held at MIT and Harvard’s Broad Institute, Boor and her colleagues used a robotic mechanism to screen 57,000 different natural and synthetic compounds for their ability to inhibit the stress-responsive defenses of Listeria bacteria. The process took several days, and after identifying a total of 14 candidates that worked at effective doses, they singled out the most effective one from three that were not toxic to mammalian cells.
The star compound, mercifully abbreviated as “FPSS” (for fluoro-phenyl-styrene-sulfonamide) works by stopping the Listeria bacteria from switching on its defenses when it comes under stress. The bacteria’s repertoire of defenses are controlled by an alternative sigma factor (a protein that acts as a “switch” for certain genes) called Sigma B. In the presence of FPSS, Sigma B fails to do its job, resulting in bacteria that can no longer survive being eaten.
“Just think about all the conditions bacteria have to withstand to infect you — when I started my lab I was completely captivated by this concept,” Boor told Food Safety News. “A pathogen has to not only survive in the food, but thrive and multiply. We’re very creative at killing the bacteria in food, but that’s nothing compared to what it has to survive when eaten. First it has to survive your mouth, and then you send it to your stomach for an acid bath. Then it goes into your intestines, an anaerobic environment — no oxygen. At the very least we would need a SCUBA suit and Hazmat gear to do that.”
Without facing any stressors such as heat or stomach acid, Listeria functions under Sigma A, which essentially directs it to spend its energy on reproduction, Boor said. Sigma B takes over for Sigma A when survival is at stake, turning on more than 150 genes that help the bacteria tough-out hostile conditions.
Boor’s laboratory was the first to report on the function of Listeria under Sigma B, which also controls genes in several other bacteria, including Staphylococcus aureus (cause of Staph infections). Boor said FPSS could likely treat other pathogens the way it does Listeria.
For now, Boor stressed that a therapeutic cure to Listeria infection was still far from becoming reality. Her next step is to delve into the interaction between FPSS and Sigma B, probing for new ways to control bacteria.
But Boor did say that one of the most exciting parts of her research is that FPSS already works within acceptable antibiotic ranges — great news for researchers looking to eventually develop therapeutics.
The U.S. Centers for Disease Control and Prevention (CDC) estimate that 1,600 cases of Listeria infection occur in the U.S. each year. Despite the relatively low number of listeriosis cases, Listeria ranks as one of the deadliest known pathogens, Boor reiterated. And unlike most other foodborne bacteria, Listeria can multiply under refrigeration.
Of particular concern for contamination have been ready-to-eat foods such as luncheon and deli meats, or other foods that aren’t reheated before eating. Until this year, a Listeria outbreak had never been linked to whole cantaloupes.
“The outbreak of Listeria in cantaloupes illustrated how much we still have to learn about the bacteria,” Boor said. “This [discovery with FPSS] adds a whole new tool to our arsenal. The compound really shows considerable promise as a therapeutic down the road, but right now it’s helping us understand the vulnerabilities of microbes like Listeria that have these incredible survival properties.”
Read more in the study’s online abstract.
Kathryn Boor photo courtesy of Cornell University.