The leaves of the European sweet chestnut are considered a traditional remedy for skin infections and inflammation in rural areas of Italy. This inspired researchers to search for medicinally effective substances in the leaves. With success: the discovered molecule Castaneroxy A disrupts the communication of MRSA bacteria and prevents these multi-resistant hospital germs from producing their harmful poison. In the mouse experiment, the agent relieved MRSA infections without promoting resistance.
The bacterium methicillin-resistant Staphylococcus aureus (MRSA) is feared as a hospital germ because it is resistant to numerous antibiotics. For many people, Staphylococcus aureus occurs as part of the natural bacterial flora without causing any problems. However, especially in people with a weakened immune system, the bacterium can multiply on a massive scale and cause serious infections, some of which are fatal.
Traditional medicine as inspiration
A team led by Akram Salam from Emory University in Atlanta has now discovered a possible active ingredient against MRSA infections. “In view of increasing antibiotic resistance, the world needs new drugs against infectious diseases,” the researchers write. “All previously approved antibiotic treatments work by killing the bacteria or inhibiting their growth.” However, this promotes resistance, since the bacteria that manage to escape the antibiotic have a strong selection advantage.
Salam and his colleagues have now found a possible alternative through research in the field of naturopathy: “In traditional Italian medicine, a compress made from the cooked leaves of the sweet chestnut is placed on the skin to treat burns, rashes and infected wounds,” explains Salams Colleague Cassandra Quave. The researchers then examined samples from the leaves of the sweet chestnut (Castanea sativa) and identified medically effective substances.
Molecule renders bacteria harmless
And indeed: A newly discovered molecule, which the researchers named Castaneroxy A, renders MRSA bacteria harmless without promoting resistance. “We showed how the active ingredient disarms methicillin-resistant Staphylococcus aureus by switching off the ability of bacteria to produce toxins,” reports Quave. This ability is what makes Castaneroxy A special compared to conventional antibiotics: since it does not inhibit the growth and survival of bacteria, it does not contribute to the development of resistance. Instead, it disrupts the bacteria ‘communication, prevents them from producing toxins, and reduces their virulence.
“We were able to isolate this molecule and get pure crystals from it, even though it only makes up 0.0019 percent of the chestnut leaves,” says Quave. In order to develop drugs based on this active ingredient in the future, the researchers clarified the three-dimensional crystal structure of the molecule – and thus also provided the basis for modifications that could make the active ingredient even more effective. “Whether Castaneroxy A can successfully improve the therapeutic results in the treatment of MRSA infections – either alone or as a supplement to antibiotics – remains to be seen,” the researchers write.
Successful tests on mice
However, a test on mice provides an initial indication of the therapeutic effectiveness. The researchers infected open wounds in the skin of the mice with MRSA and treated some of the animals with different doses of the newly discovered active ingredient. The result: While the wounds of the untreated mice became infected, parts of the skin died and some animals succumbed to the infection, the injuries of the treated mice healed significantly better – more effectively with a dose of 50 micrograms of the active ingredient than with a dose of 10 Micrograms.
Tests on human skin cells also showed that Castaneroxy A has a cytotoxic effect at very high concentrations, but that the active ingredient is probably harmless in a concentration sufficient to effectively inhibit MRSA. “We are laying the foundation for new strategies to combat bacterial infections at the clinical level,” says Quave. “Instead of worrying too much about treating the pathogen, we focus 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 an infection. “
Source: Akram Salam (Emory University, Atlanta, USA) et al., Frontiers in Pharmacology, doi: 10.3389 / fphar.2021.640179