Brazilian Peppertree Photo by: Forest and Kim Starr, via WikiMedia Commons
Researchers from Emory University in Atlanta have isolated two triterpenoid acids that appear to inhibit the ability of methicillin-resistant Staphylococcus aureus (MRSA) to produce the tissue-damaging toxins that impair wound healing. The two triterpenoid acids were isolated from the fruit of the Brazilian Peppertree, an invasive shrub in Florida, according to findings published in Scientific Reports (May 15, 2020). “It is a noxious weed that many people in Florida hate, for good reason,” lead researcher Cassandra Quave, PhD, said in a press release. “But, at the same time, there is this rich lore about the Brazilian Peppertree in the Amazon, where traditional healers have used the plant for centuries to treat skin and soft tissue infections.” Because these agents prevent expression of genes in MRSA that allow it to excrete toxins, rather than killing the bacteria, it is thought that they will not spur the development of treatment-resistant strains. Ethnobotanist Dr. Quave is a member of the Emory Antibiotic Resistance Center. She and her team had previously found, in 2017, that a flavone-rich mix of 27 compounds extracted from the berries inhibited formation of skin lesions in mice infected with MRSA. In the new study, the team refined the individual components from the original 27-compound mixture and tested the potency of each against MRSA. The team also used a series of analytical chemistry techniques, including mass spectrometry, nuclear magnetic resonance spectroscopy and X-ray crystallography to gain a clear picture of the chemicals involved in the anti-virulence mechanism. They found that three triterpenoid acids worked equally well at inhibiting MRSA from forming toxins in a petri dish, without harming human skin cells. As well, one of the triterpenoid acids worked particularly well at inhibiting the ability of MRSA to form lesions on the skin of mice. The researchers also demonstrated that the triterpenoid acids repressed not just one gene that MRSA uses to excrete toxins, but two genes involved in that process. “Nature is the best chemist, hands down,” Dr. Quave said. She noted that weeds, in particular, tend to have interesting chemical arsenals that they may use to protect them from diseases so they can more easily spread in new environments. Further studies of the triterpenoid acids as treatments for MRSA infections are planned in animal models. “Plants are so incredibly complex chemically that identifying and isolating particular extracts is like picking needles out of haystacks,” Dr. Quave said. “When you’re able to pluck out molecules with medicinal properties from these complex natural mixtures, that’s a big step forward to understanding how some traditional medicines may work, and for advancing science toward a potential drug development pathway.”