The European chestnut, Castanea sativa.
The leaves contain a chemical that neutralises MRSA by blocking its ability to make toxins.
The leaves contain a chemical that neutralises MRSA by blocking its ability to make toxins.
Another example today of why maintaining biodiversity is important...
Scientists have isolated a chemical from the leaves of the European sweet chestnut tree which could prove invaluable in our arms race with MRSA. They have called this substance, castaneroxy A, after the Latin name for the sweet chestnut tree, Castanea sativa.
According to Carol Clarke, writing in Emory University eScienceCommons:
Scientists isolated a molecule, extracted from the leaves of the European chestnut tree, with the power to neutralize dangerous, drug-resistant staph bacteria. Frontiers in Pharmacology published the finding, led by scientists at Emory University.Their findings are published, open access, in the online Journal, Frontiers in Pharmacology:
We were able to isolate this molecule, new to science, that occurs only in very tiny quantities in the chestnut leave. We also showed how it disarms Methicillin-resistant Staphylococcus aureus by knocking out the bacteria’s ability to produce toxins.The researchers dubbed the molecule Castaneroxy A, after the genus of the European chestnut, Castanea. The use of chestnut leaves in traditional folk remedies in rural Italy inspired the research.
We’re trying to fill the pipeline for antimicrobial drug discovery with compounds that work differently from traditional antibiotics. We urgently need these new strategies.
We’re laying the groundwork for new strategies to fight bacterial infections at the clinical level. 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.
Cassandra Quave, senior author.
Associate professor
Center for the Study of Human Health
And the School of Medicine, Department of Dermatology.
Emory University, Atlanta, GA, USA
“We were able to isolate this molecule, new to science, that occurs only in very tiny quantities in the chestnut leaves,” says Cassandra Quave, senior author of the paper and associate professor in Emory’s Center for the Study of Human Health and the School of Medicine’s Department of Dermatology. “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) causes infections that are difficult to treat due to its resistance to antibiotics. It is one of the most serious infectious disease concerns worldwide, labeled as a “serious threat” by the Centers for the Disease Control and Prevention. In the United States alone, nearly 3 million antibiotic-resistant infections occur in the U.S. each year, killing more than 35,000 people.
Antibiotics work by killing staph bacteria, which can lead to greater resistance among those few bacteria that survive, spawning “super bugs.” The Quave lab has identified compounds from the Brazilian peppertree, in addition to the European chestnut tree, that simply neutralize the harmful effects of MRSA, allowing cells and tissue to naturally heal from an infection without boosting resistance.
“We’re trying to fill the pipeline for antimicrobial drug discovery with compounds that work differently from traditional antibiotics,” Quave says. “We urgently need these new strategies.” She notes that antimicrobial infections kill an estimated 700,000 globally each year, and that number is expected to grow exponentially if new methods of treatment are not found.
Methicillin-resistant Staphylococcus aureus (MRSA) represents one of the most serious infectious disease concerns worldwide, with the CDC labeling it a “serious threat” in 2019. The current arsenal of antibiotics works by targeting bacterial growth and survival, which exerts great selective pressure for the development of resistance. The development of novel anti-infectives that inhibit quorum sensing and thus virulence in MRSA has been recurrently proposed as a promising therapeutic approach. In a follow-up of a study examining the MRSA quorum sensing inhibitory activity of extracts of Italian plants used in local traditional medicine, 224C-F2 was reported as a bioactive fraction of a Castanea sativa (European chestnut) leaf extract. The fraction demonstrated high activity in vitro and effective attenuation of MRSA pathogenicity in a mouse model of skin infection. Through further bioassay-guided fractionation using reverse-phase high performance liquid chromatography, a novel hydroperoxy cycloartane triterpenoid, castaneroxy A (1), was isolated. Its structure was established by nuclear magnetic resonance, mass spectrometry and X-ray diffraction analyses. Isomers of 1 were also detected in an adjacent fraction. In a series of assays assessing inhibition of markers of MRSA virulence, 1 exerted activities in the low micromolar range. It inhibited agr::P3 activation (IC50 = 31.72 µM), δ-toxin production (IC50 = 31.72 µM in NRS385), supernatant cytotoxicity to HaCaT human keratinocytes (IC50 = 7.93 µM in NRS385), and rabbit erythrocyte hemolytic activity (IC50 = 7.93 µM in LAC). Compound 1 did not inhibit biofilm production, and at high concentrations it exerted cytotoxicity against human keratinocytes greater than that of 224C-F2. Finally, 1 reduced dermonecrosis in a murine model of MRSA infection. The results establish 1 as a promising antivirulence candidate for development against MRSA.The problem is that, without these speculative investigations we have no way of knowing what potentially invaluable resources there might be in the living world around us, and no way of predicting it either. So, it is essential that we conserve as much of what biodiversity we have left. Nature has been indulging in myriads of arms races with pathogens and parasites for millions of years, so it would be astonishing if there were not hundreds of potential allies in our own arms races that we can harvest and learn from.
Salam, Akram M.; Porras, Gina; Cho, Young-Saeng K.; Brown, Morgan M.; Risener, Caitlin J.; Marquez, Lewis; Lyles, James T.; Bacsa, John; Horswill, Alexander R.; Quave, Cassandra L. br> Castaneroxy A From the Leaves of Castanea sativa Inhibits Virulence in Staphylococcus aureus.
Front. Pharmacol. 12, 640179 (2021). DOI: 10.3389/fphar.2021.640179
Copyright: © 2021 The authors. Published by Frontiers Media S.A.
Open access
Reprinted under a Creative Commons Attribution 4.0 International License (CC BY 4.0)
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