Extracts made from the leaves of the European chestnut tree Castanea sativa have been used in traditional medicine for more than 100 years. Researchers have shown that these extracts can prevent methicillin-resistant Staphylococcus aureus (MRSA) from producing a variety of dangerous toxins and can halt skin infections in mice, but they didn’t know which molecule or molecules were responsible for keeping the bacterium at bay until now.
Researchers led by Emory University’s Cassandra L. Quave have identified a new compound, which they named castaneroxy A, as the key antibacterial compound. They also found that, like the leaf extract, castaneroxy A blocks MRSA skin infections from progressing in mice (Front. Pharmacol. 2021, DOI: 10.3389/fphar.2021.640179).
While all antibiotic drugs approved by the US Food and Drug Administration work by killing bacteria or preventing bacterial growth, Quave and colleagues found that castaneroxy A has a different mechanism: it disrupts quorum sensing—chemical communication that bacteria use to coordinate infection. Scientists have speculated that bacteria will have a tough time evolving resistance to therapies that block quorum sensing because this strategy doesn’t kill bacteria; drugs that kill bacteria can leave behind drug-resistant mutants to thrive.
S. aureus controls quorum sensing using its accessory gene regulator (agr) system, and castaneroxy A appears to muck up this system. “Small molecules that modulate the activity of the agr system in S. aureus are relatively rare, so Quave and coworkers have made an exciting finding,” says Helen E. Blackwell, an expert in quorum sensing at the University of Wisconsin-Madison, in an email. She adds that it will be important to unravel how castaneroxy A interacts with the agr system.
Next, Quave would like to test casternoxy A’s ability to fight other types of MRSA infections in animals, including bloodstream infections and pneumonia. She also plans to continue hunting for medicinal molecules from plants. “There are over 33,000 species of plants that have been used in some form of traditional medicine,” Quave says. “We’ve just barely scratched the surface of investigating” their pharmacological potential.