UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Insertion of epicatechin gallate into the cytoplasmic membrane of methicillin-resistant Staphylococcus aureus disrupts penicillin-binding protein (PBP) 2a-mediated beta-lactam resistance by delocalizing PBP2.

Bernal, P; Lemaire, S; Pinho, MG; Mobashery, S; Hinds, J; Taylor, PW; (2010) Insertion of epicatechin gallate into the cytoplasmic membrane of methicillin-resistant Staphylococcus aureus disrupts penicillin-binding protein (PBP) 2a-mediated beta-lactam resistance by delocalizing PBP2. J Biol Chem , 285 (31) 24055 - 24065. 10.1074/jbc.M110.114793. Green open access

[thumbnail of insertion.pdf]
Preview
PDF
insertion.pdf
Available under License : See the attached licence file.

Download (1MB)

Abstract

Epicatechin gallate (ECg) sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin and other beta-lactam agents; it also reduces the secretion of virulence-associated proteins, prevents biofilm formation, and induces gross morphological changes in MRSA cells without compromising the growth rate. MRSA is resistant to oxacillin because of the presence of penicillin-binding protein 2a (PBP2a), which allows peptidoglycan synthesis to continue after oxacillin-mediated acylation of native PBPs. We show that ECg binds predominantly to the cytoplasmic membrane (CM), initially decreasing the fluidity of the bilayer, and induces changes in gene expression indicative of an attempt to preserve and repair a compromised cell wall. On further incubation, the CM is reorganized; the amount of lysylphosphatidylglycerol is markedly reduced, with a concomitant increase in phosphatidylglycerol, and the proportion of branched chain fatty acids increases, resulting in a more fluid structure. We found no evidence that ECg modulates the enzymatic activity of PBP2a through direct binding to the protein but determined that PBP2 is delocalized from the FtsZ-anchored cell wall biosynthetic machinery at the septal division site following intercalation into the CM. We argue that many features of the ECg-induced phenotype can be explained by changes in the fluid dynamics of the CM.

Type: Article
Title: Insertion of epicatechin gallate into the cytoplasmic membrane of methicillin-resistant Staphylococcus aureus disrupts penicillin-binding protein (PBP) 2a-mediated beta-lactam resistance by delocalizing PBP2.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1074/jbc.M110.114793
Publisher version: http://dx.doi.org./10.1074/jbc.M110.114793
Language: English
Additional information: PMCID: PMC2911331 © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Free via Creative Commons: CC Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License applies to Author Choice Articles
Keywords: Anisotropy, Anti-Bacterial Agents, Catechin, Cell Wall, Cytoplasm, Drug Resistance, Bacterial, Gene Expression Regulation, Bacterial, Lysine, Methicillin, Methicillin-Resistant Staphylococcus aureus, Microscopy, Fluorescence, Oligonucleotide Array Sequence Analysis, Penicillin-Binding Proteins, Phosphatidylglycerols, beta-Lactams
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/1350909
Downloads since deposit
58Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item