The natural world is full of microbes, fungi, and plants that have given us valuable medicines, like tetracyclines, penicillin, and morphine. Researchers have now identified a molecule they called Castaneroxy A in leaves from the European chestnut tree. This compound can eliminate drug-resistant staphylococcus pathogens, apparently without harming healthy tissue. The work has been reported in Frontiers in Pharmacology.
"We were able to isolate this molecule, new to science, that occurs only in very tiny quantities in the chestnut leaves," said senior study author Cassandra Quave, an associate professor at Emory University. "We also showed how it disarms methicillin-resistant Staphylococcus aureus by knocking out the bacteria's ability to produce toxins."
Methicillin-resistant Staphylococcus aureus (MRSA) is one of many drug-resistant pathogens that scientists are concerned about. Almost 3 million antibiotic-resistant infections are estimated to occur in the U.S. each year, and lead to the death of over 35,000 people.
"We're trying to fill the pipeline for antimicrobial drug discovery with compounds that work differently from traditional antibiotics," Quave said. "We urgently need these new strategies." She added that 700,000 people die from bacterial infections each year, and that will only rise unless new medicines are developed.
In rural Italy, chestnut leaves are known as a folk remedy. Quave and her research team began this work over ten years ago by conducting field interviews that led the research team to the antimicrobial compound.
"In Italian traditional medicine, a compress of the boiled [chestnut tree] leaves is applied to the skin to treat burns, rashes and infected wounds," noted Quave.
In 2015, the Quave lab reported that an extract from the leaves could eliminate serious MRSA infections in otherwise healthy people, and did so without harming nearby. healthy cells.
They found that the extract disrupted the ability of MRSA pathogens to signal to one another; that process, called quorum sensing, enables the pathogenic bacterial colony to mount a major infection and produce lots of toxins.
In this work, the researchers painstakingly isolated each chemical in the extract, even custom building a machine to do so to their specifications, and within budget. That work revealed that cycloartane triterpenoids diminished MRSA's virulence. Additional work showed that Castaneroxy A was the most active of these compounds.
When the study investigators tested Castaneroxy A on a mouse model of MRSA, the infection stopped and the skin healed.
"We're laying the groundwork for new strategies to fight bacterial infections at the clinical level," Quave said. "Instead of being overly concerned about treating the pathogen, we're focusing on ways to better treat the patient. Our goal is not to kill the microbes but to find ways to weaken them so that the immune system or antibiotics are better able to clear out an infection."