In the southern United States, the Brazilian peppertree is no one’s garden favorite.
Officially classified as a noxious weed in Florida, the tall, aggressive invader is a distant relative of poison ivy. It’s loaded with irritating compounds that some people react to just from smelling its flowers.
Yet the despised peppertree might turn out to be medically valuable. An Emory University researcher has identified a compound in its fruit that possesses a novel mechanism for controlling antibiotic resistance, one of the greatest threats to public health.
Cassandra Quave is an assistant professor of dermatology and human health at Emory and an ethnobotanist with a special interest in recovering lost botanical remedies. Such homemade medications are backed by centuries of folk wisdom but often ignored by modern pharmaceutical chemistry.
Quave’s earlier work focused on southern Italy and Albania, but she happens to come from Florida, “and I came across the peppertree all the time in my childhood, because it grows near my dad’s place,” she says.
Also known as Christmas berry for its brilliant fuchsia fruit and glossy green leaves, Schinus terebinthifolius can tower up to 30 feet. It colonizes land and water rapidly, and its branches grow so densely that it blocks light for other plants and for fish. It was imported, at first, to be grown for ornamental cuttings, but now it is so out of control that it is illegal to sell or move one in Florida.
“It’s hated down there,” says Quave. “But in Brazil, there are accounts of it being used as a medication that go back hundreds of years.”
Silencing a Killer
In the peppertree’s fleshy fruit, Quave and her collaborators at Emory and the University of Iowa found a compound that has an unusual and valuable property. Instead of destroying bacteria—which most antibiotics do, and which most bacteria have evolved protections against—the extract prevents bacteria from talking to each other.
That provides a novel means of controlling MRSA, the drug-resistant form of staph bacteria. MRSA infections alone account for more than 11,000 deaths in the United States each year, a significant portion of the 23,000 deaths and 2 million serious infections attributed to antibiotic resistance by the U.S. Centers for Disease Control and Prevention.
The key is that MRSA behaves differently when it is burgeoning into a colony than when it exists as random individual cells.
In a colony, MRSA cells communicate to organize the production of a range of toxins that cause skin and blood cells to explode, launching a cascade of tissue destruction. But if the MRSA cells’ communication, called quorum sensing, is blocked, the toxins are not produced.
And because the compound isn’t directly attacking the bacteria, there is nothing to provoke their descendants into developing resistance.
As they describe in Scientific Reports, Quave and her team found that their compound, which they are describing as a “quorum quencher,” contains a complex mix of plant chemicals that shut down the activity of a set of genes that direct cell communication.
They tested the effect on human and mouse skin cells, and also on living mice which they injected with MRSA. The mice that did not receive the peppertree extracts developed staph skin lesions; the mice that got the novel compounds did not.
“The bacteria are still living—they are there—but they are not able to induce their toxin production system, so you don’t see the damage to tissue,” she says. “So we can prevent progression of toxin-mediated disease.”
New Drugs From Old Sources
Freya Harrison, a microbiologist and assistant professor at the University of Warwick, says Quave’s work demonstrates that the plant kingdom, once the source of all pharmaceuticals, contains useful, novel compounds.
“Everything now has gone to synthetic chemistry,” she says. “But plants are fantastic chemical factories, and folk and historical medical texts can point us to new plants to mine for new molecules.”
Harrison is a member of the U.K.-based Ancientbiotics project, which in 2015 reproduced a 1,000-year-old MRSA remedy from a medieval text held in the British Library. That experience, she says, showed why proving the scientific basis of old remedies is so hard.
“You need to be able to do ethnopharmacology and understand what the old texts are saying,” she says. “There will be a lot of placebo and a lot of things that might be dangerous, so you need to be able to spot what is scientifically sensible. Then you need skills in chemistry and pharmacology, to know what are the potentially active compounds. And you need skills in microbiology and tissue culture, to be able to say that their effects are on bacteria and human cells.”
The work of Quave and her collaborators “covers all those bases,” Harrison says.
Antibiotics are notorious for taking a long, slow path to market, but the berry-based treatment could be developed through the Botanical Drug Pathway, an under-used application process that the Food and Drug Administration created a decade ago to streamline approvals for plant-based products.
Quave and her collaborators don’t plan to pursue immediate approval, though. She envisions the components of the compound possibly being used as an adjuvant—giving a medical boost to classical antibiotics by keeping bacteria from burgeoning while antimicrobials kill them. That will require more research to tease apart the components, as well as testing each of them in lab models that mimic the situations where they might be useful, from sepsis to chronic wounds such as diabetic foot ulcers.
In the meantime, the peppertree results—like earlier work that Quave and her collaborators performed with extracts from the European chestnut tree—are vindication of her belief that science can benefit from folk knowledge.
“Here we have something that has been in use, effectively in clinical trials, for possibly thousands of years—certainly for several hundred,” she says. “We are showing that plants can be effective in treating infectious diseases, just not in the way that we have thought antibiotics or anti-infectives should work.”