Mechanisms of Action of Corilagin and Tellimagrandin I That Remarkably Potentiate the Activity of β‐Lactams against Methicillin‐Resistant Staphylococcus aureus

• DOI: 10.1111/j.1348-0421.2004.tb03489.x
• Publication Date: 2013-11-14T15:09:54Z
• Authors: Sumiko Shiota; Masato Shimizu; Jun'ichi Sugiyama; Yuji Morita; Tohru Mizushima; Tomofusa Tsuchiya
• Keywords: Boron Compounds; Staphylococcus aureus; 0303 health sciences; Drug Synergism; Microbial Sensitivity Tests; Penicillins; Muramoylpentapeptide Carboxypeptidase; beta-Lactams; Hydrolyzable Tannins; beta-Lactamases; Anti-Bacterial Agents; 3. Good health; 03 medical and health sciences; Bacterial Proteins; Glucosides; Hexosyltransferases; Gallic Acid; Peptidyl Transferases; Penicillin-Binding Proteins; Methicillin Resistance; Carrier Proteins; Oxacillin; Protein Binding

AbstractCorilagin and tellimagrandin I are polyphenols isolated from the extract of Arctostaphylos uvaursi and Rosa canina L. (rose red), respectively. We have reported that corilagin and tellimagrandin I remarkably reduced the minimum inhibitory concentration (MIC) of β‐lactams in methicillin‐resistant Staphylococcus aureus (MRSA). In this study, we investigated the effect of corilagin and tellimagrandin I on the penicillin binding protein 2′ (2a) (PBP2′ (PBP2a)) which mainly confers the resistance to β‐lactam antibiotics in MRSA. These compounds when added to the culture medium were found to decrease production of the PBP2′ (PBP2a) slightly. Using BOCILLIN FL, a fluorescent‐labeled benzyl penicillin, we found that PBP2′ (PBP2a) in MRSA cells that were grown in medium containing corilagin or tellimagrandin I almost completely lost the ability to bind BOCILLIN FL. The binding activity of PBP2 and PBP3 were also reduced to some extent by these compounds. These results indicate that inactivation of PBPs, especially of PBP2′ (PBP2a), by corilagin or tellimagrandin I is the major reason for the remarkable reduction in the resistance level of β‐lactams in MRSA. Corilagin or tellimagrandin I suppressed the activity of β‐lactamase to some extent.