title: Mechanisms of action of corilagin and tellimagrandin I that remarkably potentiate the activity of beta-lactams against methicillin-resistant Staphylococcus aureus.
abstract: Corilagin 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 beta-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 beta-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 beta-lactams in MRSA. Corilagin or tellimagrandin I suppressed the activity of beta-lactamase to some extent.
authors.affiliation: Department of Pathogenic Microbiology, School of Pharmacy, Shujitsu University, Okayama, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Shiota
authors.forename: Masato
authors.initials: M
authors.lastname: Shimizu
authors.forename: Jun'ichi
authors.initials: J
authors.lastname: Sugiyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morita
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
authors.forename: Tomofusa
authors.initials: T
authors.lastname: Tsuchiya
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism; D001896:Boron Compounds / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D004357:Drug Synergism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D006602:Hexosyltransferases / Q000096:biosynthesis / Q000378:metabolism; D047348:Hydrolyzable Tannins; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000096:biosynthesis / Q000378:metabolism; D010068:Oxacillin / Q000494:pharmacology; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010458:Peptidyl Transferases / Q000096:biosynthesis / Q000378:metabolism; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C118961:BOCILLIN FL; D001426:Bacterial Proteins; D001896:Boron Compounds; D002352:Carrier Proteins; D005960:Glucosides; D047348:Hydrolyzable Tannins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D047090:beta-Lactams; C049096:corilagin; D005707:Gallic Acid; C087926:tellimagrandin I; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; D010068:Oxacillin