title: The beta-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 beta-lactam antibiotics, promotes staphylococcal cell aggregation and increases cell-wall thickness. The potentiation of beta-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 beta-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 beta-lactam-resistant phenotype.
authors.affiliation: Microbiology Group, School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Stapleton
authors.affiliation: Microbiology Group, School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Saroj
authors.initials: S
authors.lastname: Shah
authors.affiliation: Bayer Healthcare AG, Pharma Research Center, D-42096 Wuppertal, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ehlert
authors.affiliation: Mitsui Norin Co. Ltd, 1-2-9 Nishi-Shinbashi, Minato-Ku, Tokyo 105-8427, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Microbiology Group, School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Taylor
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D018440:beta-Lactam Resistance / Q000187:drug effects* / Q000502:physiology
chemical_list: D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D002392:Catechin; C062669:epicatechin gallate