New molecules in chestnut leaves leave dangerous staphylococci for disarmament

Scientists have the power to isolate molecules extracted from the leaves of European chestnut trees and neutralize dangerous and drug-resistant staphylococci. Pharmacology frontier We have published the results of a study led by scientists at Emory University.

Researchers have named it the molecular castaneroxy A, named after the genus Castanea, a genus of sweet chestnuts. The use of chestnut leaves in traditional folk remedies in the Italian countryside has influenced the study.

“We were able to scientifically isolate this new molecule, which is present in very small amounts in chestnut leaves,” said Cassandra, senior author of the treatise and associate professor at the Center for Human Health Research, Emory University. I am. Department of Dermatology, School of Medicine. “We also showed how to disarmament methicillin-resistant Staphylococcus aureus by knocking out the ability of bacteria to produce toxins.”

Methicillin-resistant Staphylococcus aureus (MRSA) causes infections that are difficult to treat due to resistance to antibiotics. This is one of the most serious infectious disease concerns in the world and has been labeled as a “serious threat” by the US Centers for Disease Control and Prevention. In the United States alone, nearly 3 million antibiotic-resistant infections occur each year, killing more than 35,000 people.

Antibiotics work by killing staphylococci. Staphylococci increase the resistance of the few surviving bacteria and create “super bugs.” In addition to the sweet chestnut tree, Quave Labs has identified compounds from the Brazilian pepper tree that simply neutralize the harmful effects of MRSA and naturally heal cells and tissues from infection without increasing resistance.

“We are trying to fill our pipeline for the discovery of antimicrobials with compounds that work differently than traditional antibiotics,” says Quave. “We are in urgent need of these new strategies.” She kills an estimated 700,000 people worldwide each year from antibiotic infections, and if no new treatment is found, that number is an exponential function. .. It is expected to increase.

Leading author Pharmacology frontier The treatise is Akram Salam with a PhD. Quave Labs students through Emory’s Graduate Program in Molecular Systems and Pharmacology.

Quave is a medical ethnobotanist who studies traditional phytotherapy and finds promising leads for new drugs. From aspirin (willow bark) to taxol (Pacific yew bark), many major drugs are plant-based, but Quave is one of the few ethnobotanists focused on antibiotic resistance.

The story behind the current treatise began more than a decade ago, when Quave and her colleagues investigated written reports and conducted hundreds of field interviews among rural people in Southern Italy. It pointed them to European or sweet chestnut trees native to Southern Europe and Asia Minor. “In traditional Italian medicine, boiled leaf compresses are applied to the skin to treat burns, rashes and infected wounds,” says Quave.

Quave returned the specimen to the lab for analysis. By 2015, her lab announced the discovery that leaf extracts disarm even highly toxic MRSA strains that can cause serious infections in healthy athletes. Experiments have also shown that the extract does not interfere with normal and healthy bacteria on skin cells.

Finally, researchers demonstrated how the extract works by blocking the ability of MRSA bacteria to communicate with each other. This is a process called quorum sensing. MRSA uses this sensing signal system to produce toxins and increase their toxicity.

In the current treatise, researchers wanted to separate these active ingredients from plant extracts. This process can be a daunting task, as plant extracts usually contain hundreds of different chemicals. Each chemical must be separated before it can be tested for effectiveness. A high-capacity fraction collector, combined with a high-performance liquid chromatography system, automates this separation process, which can cost tens of thousands of dollars and has all the features needed for a Quave lab. Not. did.

Marco Capto, a research specialist in the lab, has solved the problem. Using children’s toy software devices, Lego Mindstorms robot creators, some Lego blocks, and some components of the hardware store, Caputo has 500 automatic liquid separators customized to the needs of the lab. We offer in dollars. I made it. Lab members call this invention the LEGO Mindstorms Fraction Collector. They have published instructions in the journal on how to build it so that other researchers can take advantage of simple and effective technology.

Quave Labs first isolated a group of molecules from the plant extract cycloaltantriterpenoids and showed for the first time that this group actively blocks the pathogenicity of MRSA. Researchers then went deeper and isolated the most active single molecule from this group, now known as castaneroxy A.

“Our homemade equipment really helped accelerate the pace of our discoveries,” says Quave. “This molecule makes up only .0019% of chestnut leaves, but can be separated into pure crystals.”

A skin test of MRSA-infected mice conducted in the laboratory of Alexander Horswill, a co-author of the University of Colorado, confirmed the effectiveness of a molecule that can block the pathogenicity of MRSA and heal the skin more quickly. it was.

Co-author John Bassa, director of the X-ray Crystallography Center in the Department of Emory Chemistry, characterized the crystal shape of castaneroxy A. Understanding the three-dimensional composition of crystals is important for future research in purifying and optimizing molecules as potential therapeutic agents. Agent. ..

“We are laying the foundation for a new strategy to combat bacterial infections at the clinical level,” says Quave. “We are focusing on ways to treat patients better, rather than being overly concerned about treating pathogens. Our goal is not to kill microbes, but to the immune system and antibiotics. Better elimination is to find a way to weaken the microbes.