Grape seed extract inhibits the growth and pathogenicity of Staphylococcus aureus by interfering with dihydrofolate reductase activity and folate-mediated one-carbon metabolism

Staphylococcus aureus (S. aureus) is one of the most common pathogens that causes infectious and foodborne diseases worldwide. Searching for drug and chemical compounds against this bacterium is still in demand. We found that grape seed extract (GSE), a natural food product rich in polyphenols, inhibited the dihydrofolate reductase activity and growth of S. aureus. In addition, the intracellular content of tetrahydrofolate (THF), the major folate species identified in S. aureus, was significantly decreased when GSE was present in medium. The GSE-induced growth inhibition was reversed by adding, THF, 5,10-methylenetetrahydrofolate or methionine to the medium. The differential rescuing effects elicited by thymidine and methionine indicated that GSE-induced perturbation in folate-mediated one-carbon metabolism has more profound impact on methionine cycle than on thymidine monophosphate (TMP) synthesis. Significantly reduced inflammatory responses and mortality were observed in zebrafish infected with S. aureus pre-incubated with GSE. We conclude that GSE might serve as an effective natural alternative for the control of food poisoning caused by S. aureus with proper safety measure.