Mechanisms of Action of Corilagin and Tellimagrandin I That Remarkably Potentiate the Activity of β‐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 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.

Xanthoradones, new potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus, produced by Penicillium radicum FKI-3765-2: I. Taxonomy, fermentation, isolation and biological properties

“…Several compounds have been reported to potentiate b-lactam activity against MRSA: polyoxotungstates, 11 polyphenols such as epigallocatechin gallate isolated from tea, 12 corilagin from Arctostaphylos uva-urs, 13 tellimagrandin I from rose red (Rosa canina), 13 diterpenes such as totarol isolated from totara tree 14 and synthetic MC-200,613. 15 Our research group has discovered microbial potentiators, such as stemphones from Aspergillus sp.…”

Cyslabdan, a New Potentiator of Imipenem Activity against Methicillin-resistant Staphylococcus aureus, Produced by Streptomyces sp. K04-0144

“…Accordingly, our idea of drug discovery in this study is important because such a potentiator would be applied for the decrease of the dose of these types of antibiotics. Several compounds have been reported to potentiate blactam activity against MRSA; polyoxotungstates [3], polyphenols such as epigallocatechin gallate isolated from tea [4], corilagin from Arctostaphylos uva-urs [5] and tellimagrandin I from rose red (Rosa canina) [5] and diterpenes such as totarol isolated from totara tree [6], and synthetic MC-200,613 [7]. Among these compounds, the structures of totarol, MC-200,616 and a part of cyslabdan are labdane-type diterpenes.…”

Stemphones, Novel Potentiators of Imipenem Activity against Methicillin-resistant Staphylococcus aureus, Produced by Aspergillus sp. FKI-2136

“…Polyphenols such as epigallocatechin gallate isolated from tea [20], corilagin [21] and tellimagrandin I [22] were also reported to show the activity. They were considered to inhibit the function of PBP2Ј and suppress b -lactamase activity [23]. The potentiating activity of various b-lactams against MRSA by stemphone and the mechanism of the potentiation activity are under investigation and will be published in the near future.…”