Scientists have isolated a molecule from the European chestnut tree's leaves that can neutralize drug-resistant, dangerous staph bacteria. The discovery was published in Frontiers in Pharmacology by Emory University scientists.
Castaneroxy A was the name given to the molecule by the researchers, in honor of Castanea, the European chestnut genus. This research was inspired by the traditional folk remedies that chestnut leaves are used in in rural Italy.
"We were able ot isolate this molecule, which is new to science that occurs only in very small quantities in the chestnut leaf," Cassandra Quave (senior author of the paper) says. She is also an associate professor at Emory's Center for the Study of Human Health. "We also demonstrated how it disarms Methicillin resistant Staphylococcus Aureus by destroying the bacteria's ability produce toxins."
MRSA (methicillin-resistant Staphylococcus Aureus) is a type of infection that resists antibiotics and can make it difficult to treat. The Centers for Disease Control and Prevention consider it a serious threat to public health. Nearly 3 million people are infected with antibiotic-resistant bacteria each year in the United States. This is more than 35,000 deaths annually.
Antibiotics kill staph bacteria. This can increase resistance and lead to more "super bugs" being born. The Quave laboratory has discovered compounds in the Brazilian peppertree and the European chestnut trees that neutralize MRSA's harmful effects. This allows cells and tissues to naturally heal from infection, without increasing resistance.
Quave states, "We are trying to fill our pipeline for antimicrobial drugs discovery with compounds that function differently from traditional antibiotics." These new strategies are urgently needed. She points out that global antimicrobial infections cause the death of approximately 700,000. This number will only increase if new treatment methods are discovered.
Akram Salam is the first author of Frontiers in Pharmacology's paper. He did the research while a Ph.D student in the Quave laboratory through Emory’s Molecular Systems and Pharmacology Graduate Program.
Quave is a medical and ethnobotanist who studies traditional plant remedies in order to discover promising new drug leads. Quave, despite the fact that many of the most popular drugs are plant-based (from aspirin (the bark from the willow tree to Taxol) to Taxol [the bark from the Pacific yewtree tree bark], is one of few ethnobotanists who focuses on antibiotic resistance.
Quave and her coworkers began the story of the current paper more than a decade before. They researched written reports and conducted hundreds field interviews with people in rural southern Italy. This led them to the European sweet chestnut tree, a native to Southern Europe, Asia Minor. Quave explains that in traditional Italian medicine, the leaves are applied to the skin to treat burns and rashes, as well as wounds.
Quave brought specimens back from her lab to be analyzed by Quave. Her lab published in 2015 the discovery that the extract from the leaves can disarm even the most virulent MRSA strains that could cause serious infections in healthy athletes. The extract also did not disrupt normal, healthy bacteria in skin cells according to experiments.
The researchers also demonstrated that the extract inhibited MRSA bacteria's ability to communicate with each other, a process called quorum sensing. This sensing signaling system is used by MRSA to create toxins and increase its virulence.
The researchers sought to isolate the active ingredients in the plant extract for the current paper. Manually, the process can be tedious because plant extracts often contain hundreds of chemicals. Each chemical needs to be separated and tested for effectiveness. Although large-scale fraction collectors and high-performance liquidchromatographic systems automate this process, they can be expensive and do not provide all the features that the Quave laboratory needed.
Marco Caputo was a lab researcher who solved the problem. Caputo created an automated liquid separator for the lab using a LEGO MINDSTORMS robot maker software, some LEGO bricks and parts from a hardware shop. It cost $500. The invention was referred to by the LEGO MINDSTORMS Fraction Collector by the lab members. The instructions on how to construct it were published in a journal, so other researchers could benefit from the simple but powerful technology.
The first to separate a group from the plant extract, the Quave lab discovered that cycloartane Triterpenoids was active in blocking the virulence and virulence MRSA. Castaneroxy A, the most active molecule in this group, was then separated by the researchers.
Quave states that "our homemade equipment really helped speed up the pace of our discoveries." "We were able isolate this molecule from the chestnut leaves and extract pure crystals, even though it makes up only.0019 percent."
Infected mouse skin with MRSA was tested in the laboratory of Alexander Horswill, University of Colorado. The results showed that the molecule is effective in preventing the virus from virulence and allowing the skin to heal faster.
John Bacsa (director of Emory Department of Chemistry’s X-ray Crystallography Center), was a co-author who characterized Castaneroxy A's crystal structure. It is crucial to understand the three-dimensional structure of the crystal for future research that will refine and optimize the potential therapeutic properties of Castaneroxy A.
Quave states, "We're laying groundwork for new strategies in fighting bacterial infections at clinical level." We are not too concerned with the disease, but instead we focus on how to treat the patient. We don't want to kill microbes, but rather to find ways to weaken them to make it more difficult for the immune system and antibiotics to eradicate an infection.
The paper's Emory coauthors include Caitlin Risener, Lewis Marquez, post-doctoral fellow Gina Porras, and James Lyles (former staff scientist). Young-Saeng Cho, Morgan Brown and others are also from the University of Colorado.
This work was supported by the National Center for Complementary and Integrative Health. Emory's Department of Dermatology and the National Institute of Allergy and Infectious Diseases funded it.