The β-lactam-resistance modifier (−)-epicatechin gallate alters the architecture of the cell wall of Staphylococcus aureus

Abstract

(")-Epicatechin gallate (ECg), a component of green tea, sensitizes meticillin-resistant Staphylococcus aureus (MRSA) to b-lactam antibiotics, promotes staphylococcal cell aggregation and increases cell-wall thickness. The potentiation of b-lactam activity against MRSA by ECg was not due to decreased bacterial penicillin-binding protein (PBP) 2a expression or ECg binding to peptidoglycan. A 5-10 % reduction in peptidoglycan cross-linking was observed. Reduced cross-linking was insufficient to compromise the integrity of the cell wall and no evidence of PBP2a activity was detected in the muropeptide composition of ECg-grown cells. ECg increased the quantity of autolysins associated with the cell wall, even though the cells were less susceptible to Triton X-100-induced autolysis than cells grown in the absence of ECg. ECg promoted increased lysostaphin resistance that was not due to alteration of the pentaglycine cross-bridge configuration or inhibition of lysostaphin activity. Rather, decreased lysostaphin susceptibility was associated with structural changes to wall teichoic acid (WTA), an acid-labile component of peptidoglycan. ECg also promoted lipoteichoic acid (LTA) release from the cytoplasmic membrane. It is proposed that ECg reduces b-lactam resistance in MRSA either by binding to PBPs at sites distinct from the penicillin-binding site or by intercalation into the cytoplasmic membrane, displacing LTA from the phospholipid palisade. Thus, ECg-mediated alterations to the physical nature of the bilayer will elicit structural changes to WTA that result in modulation of the cell-surface properties necessary to maintain the b-lactam-resistant phenotype.

Recent advances in understanding the antibacterial properties of flavonoids

“…Studies with model membranes indicate that flavonoids cause aggregation though [60,61], and in 2007 it was confirmed that the flavonol galangin has this effect on bacterial cells [62]. The flavan-3-ol epicatechin gallate has also been reported to cause bacterial aggregation [19], although it is not yet clear whether this observation was due to genuine aggregation (cells clumping together) or pseudomulticellular bacteria (cells failing to separate following binary fission [54]). An important ramification of this aggregatory effect is that conventional methods are no longer sufficient for demonstrating the bactericidal activity of flavonoids.…”

“…Most of the reports of flavonoids possessing antibacterial properties can be attributed to these six structures or their isoflavonoid counterparts (flavonoids where ring B is joined at position 3 of ring C instead of position 2). Potential applications for these compounds include modern agents [18] and adjuncts [19] for the treatment of bacterial infections, drugs for treating toxin-mediated disease [20], antivirulence therapies [21] and capture molecules for removing endotoxin from pharmaceutical preparations [22]. In this paper, reports on the diverse range of antibacterial properties exhibited by flavonoids are reviewed.…”

Interaction with Polyphenols and Antibiotics

“…Many studies was reported that EGCG acts synergistically with various β-lactam antibiotics against MRSA [36]. The polyphenol extract containing epicatechin gallate (ECG), EGC, EGCG, epicatechin and gallocatechin gallate from Korean green tea has antibacterial activity against 13 strains of MRSA clinical isolates and 17 strains of methicillin susceptible S. aureus (MSSA).…”

Metabolite profiling by UPLC-PDA-ESI/HDMS and antibacterial activity of Memecylon talbotianum Brandis

“…The increasing attraction for the use of phenolics as antibacterial agents maystimulate the use of these extracts as natural food preservatives, potential antibiotic replacements, and as a potential natural source of antimicrobial drugs which will provide novel or lead compounds that may be employed in controlling some infections. [28][29][30][31] CONCLUSION UPLC based metabolite analysis was employed to evaluate the chemical constituents of Eighteen metabolites were identified were synapoylhexose-formic acid, kaempferol 3-O-feruloylhexosyl rhamnoside, 6-Carabinosyl-8-C-glucosyl-apigenin and isorhamnetin-3-O-glycoside-7-O-glycoside reported for the first time from this plant. Its methanol extract showed antibacterial activity was studied in vitro.…”