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

1 Microbiology Group, School of Pharmacy, 29–39 Brunswick Square, London WC1N 1AX, UK 2 Bayer Healthcare AG, Pharma Research Center, D-42096 Wuppertal, Germany 3 Mitsui Norin Co. Ltd, 1-2-9 Nishi-Shinbashi, Minato-Ku, Tokyo 105-8427, Japan Correspondence Peter W. Taylor peter.taylor{at}pharmacy.ac.u...

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Published in:	Microbiology (Society for General Microbiology) 2007-07, Vol.153 (7), p.2093-2103
Main Authors:	Stapleton, Paul D, Shah, Saroj, Ehlert, Kerstin, Hara, Yukihiko, Taylor, Peter W
Format:	Article
Language:	eng
Subjects:	beta-Lactam Resistance - drug effects beta-Lactam Resistance - physiology Biological and medical sciences Catechin - analogs & derivatives Catechin - chemistry Catechin - pharmacology Cell Wall - chemistry Cell Wall - drug effects Cell Wall - enzymology Fundamental and applied biological sciences. Psychology Microbiology Penicillin-Binding Proteins Peptidoglycan - metabolism Staphylococcus aureus Staphylococcus aureus - drug effects Staphylococcus aureus - genetics Staphylococcus aureus - growth & development
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Summary:	1 Microbiology Group, School of Pharmacy, 29–39 Brunswick Square, London WC1N 1AX, UK 2 Bayer Healthcare AG, Pharma Research Center, D-42096 Wuppertal, Germany 3 Mitsui Norin Co. Ltd, 1-2-9 Nishi-Shinbashi, Minato-Ku, Tokyo 105-8427, Japan Correspondence Peter W. Taylor peter.taylor{at}pharmacy.ac.uk (–)-Epicatechin gallate (ECg), a component of green tea, sensitizes meticillin-resistant Staphylococcus aureus (MRSA) to β -lactam antibiotics, promotes staphylococcal cell aggregation and increases cell-wall thickness. The potentiation of β -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 β -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 β -lactam-resistant phenotype. Abbreviations: EC, (–)-epicatechin; ECg, (–)-epicatechin gallate; EGCg, (–)-epigallocatechin gallate; LTA, lipoteichoic acid; MRSA, meticillin-resistant Staphylococcus aureus ; MSSA, meticillin-susceptible S. aureus ; PBP, penicillin-binding protein; VISA, vancomycin-intermediate-resistant S. aureus ; WTA, wall teichoic acid
ISSN:	1350-0872 1465-2080