Effects of natural polyphenols on methicillin-resistant Staphylococcus aureus in relation to their chemical and physical properties

Appearance of various kinds of drug-resistant bacteria became serious problems in hospitals. Among them, methicillin-resistant Staphylococcus aureus (MRSA) have one of the most frequently found ones in Japan. Our investigation on the natural products with antibacterial effects revealed that a series of polyphenolic compounds with low or high (tannin) molecular weight have direct antibacterial effects on MRSA, and several of them have suppressive effects on the antibiotic resistance. Among those polyphenols, epigallocatechin gallate (EGCG) is unstable in solution, but its decrease does not mean the decrease of the antibacterial effect directly, and theasinensin A, an oxidation product from EGCG, also showed direct antibacterial effect and suppressive effect on the antibiotic resistance. However, the prolonged treatment of theasinensin A weakened the suppressive effect. The effects of the addition of food additive to EGCG solution for prolongation or enhancement of the effects of EGCG were examined, and ascorbic acid was the effective one for this purpose. Since mechanistic study suggested that some interference of enzyme proteins such as penicillin binding protein (PBP) 2a due to polyphenols and disturbance of bacterial lipid membrane participate in the effects of those polyphenolic compounds, interaction of polyphenols with biomolecules was also investigated, to clarify the fundamental properties of polyphenols related to the antibacterial effect, employing bovine serum albumin (BSA). The size and stability of the complex formed from polyphenols and BSA varied dependent on the structures of polyphenols. Although the differences in the properties of polyphenols in complex formation were not correlated with the antibacterial effect directly, this approach will give useful information for explaining the differences in the effects on the bacterial biomolecules.