Bernal, P., Lemaire, S., Pinho, M.G., Mobashery, S., Hinds, J. and Taylor, P.W. (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. Journal of Biological Chemistry, 285 (31). pp. 24055-24065. 10.1074/jbc.M110.114793.
Full text not available from this repository.
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.
|Departments, units and centres:||Department of Pharmaceutics > Department of Pharmaceutics|
|Journal or Publication Title:||Journal of Biological Chemistry|
|Deposited By:||Library Staff|
|Deposited On:||12 Jan 2012 11:40|
|Last Modified:||12 Jan 2012 11:40|
Item downloaded times since 12 Jan 2012 11:40.
View statistics for "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."
Repository Staff Only: Item control page
School of Pharmacy Staff Only: Edit a copy to replace this item