Cassandra Quave, Ph.D., has built a career on the medicinal properties of plants. The Emory University ethnobotanist is particularly interested in plant extracts that could be used to treat bacterial infections. Quave and University of Iowa microbiologist Alexander Horswill, Ph.D., identified chemicals from chestnut leaves (Castanea sativa) that decrease toxin production by methicillin-resistant Staphylococcus aureus (MRSA).
The team distilled chemicals from the chestnut leaves and identified 94 compounds that were active against the bacteria. The chemicals, derivatives of ursene and oleanene, disrupt the agr pathway, a key quorum sensing pathway the bacteria use to communicate with each other and produce virulence factors such as toxins. They published their findings in the journal PLOS ONE.
“Rather than killing Staph, this botanical extract works by taking away Staph’s weapons, essentially shutting off the ability of the bacteria to create toxins that cause tissue damage. In other words, it takes the teeth out of the bacteria’s bite.”
The chestnut extract works by antagonizing the S. aureus “accessory gene regulator” (agr) system. This system regulates virulence factor production through the quorum sensing molecule AIP. An excess of AIP signals the bacteria to produce virulence factors such as toxins.
The extract cleared MRSA skin lesions in mice without affecting healthy tissue or normal skin flora. Importantly, the bacteria did not become resistant to the extract, even after long-term exposure.
An obvious drawback is that these extracts do not actually kill the bacteria, they only attenuate virulence. This means that antibiotics would need to be used in conjunction with the extracts, an obvious roadblock when treating antibiotic-resistant bacteria.
Despite this shortcoming, Quave is hopeful. “We now have a mixture that works”, she says, “our goal is to further refine it into a simpler compound that would be eligible for FDA consideration as a therapeutic agent”.