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Peter W Taylor - One of the best experts on this subject based on the ideXlab platform.
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Epicatechin Gallate a naturally occurring polyphenol alters the course of infection with β lactam resistant staphylococcus aureus in the zebrafish embryo
Frontiers in Microbiology, 2015Co-Authors: Christina S Stevens, Helena Rosado, Robert J Harvey, Peter W TaylorAbstract:(-)-Epicatechin Gallate (ECg) substantially modifies the properties of Staphylococcus aureus and reversibly abrogates β-lactam resistance in methicillin/oxacillin resistant (MRSA) isolates. We have determined the capacity of ECg to alter the course of infection in zebrafish embryos challenged with epidemic clinical isolate EMRSA-16. At 30 hours post fertilization (hpf), embryos were infected by injection of 1-5 × 103 colony forming units (CFU) of EMRSA-16 into the circulation valley or yolk sac. Infection by yolk sac injection was lethal with a challenge dose above 3 × 103 CFU, with no survivors at 70 hpf . In contrast, survival at 70 hpf after injection into the circulation was 83% and 44% following challenge with 3 × 103 and 1-5 × 103 CFU respectively. No significant increases in survival were noted when infected embryos were maintained in medium containing 12.5-100 µg/mL ECg with or without 4 or 16 µg/mL oxacillin. However, when EMRSA-16 was grown in medium containing 12.5 µg/mL ECg and the bacteria used to infect embryos by either the circulation valley or yolk sac, there were significant increases in embryo survival in both the presence and absence of oxacillin. ECg-modified and unmodified, GFP-transformed EMRSA-16 bacteria were visualized within phagocytic cells in the circulation and yolk sac; pre-treatment with ECg also significantly increased induction of the respiratory burst and suppressed increases in IL-1β expression typical of infection with untreated EMRSA-16. We conclude that exposure to ECg prior to infection reduces the lethality of EMRSA-16, renders cells more susceptible to elimination by immune processes and compromises their capacity to establish an inflammatory response in comparison to non-exposed bacteria.
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impact of the β lactam resistance modifier Epicatechin Gallate on the non random distribution of phospholipids across the cytoplasmic membrane of staphylococcus aureus
International Journal of Molecular Sciences, 2015Co-Authors: Helena Rosado, Robert D Turner, Simon J Foster, Peter W TaylorAbstract:The polyphenol (−)-Epicatechin Gallate (ECg) inserts into the cytoplasmic membrane (CM) of methicillin-resistant Staphylococcus aureus (MRSA) and reversibly abrogates resistance to β-lactam antibiotics. ECg elicits an increase in MRSA cell size and induces thickened cell walls. As ECg partially delocalizes penicillin-binding protein PBP2 from the septal division site, reduces PBP2 and PBP2a complexation and induces CM remodelling, we examined the impact of ECg membrane intercalation on phospholipid distribution across the CM and determined if ECg affects the equatorial, orthogonal mode of division. The major phospholipids of the staphylococcal CM, lysylphosphatidylglycerol (LPG), phosphatidylglycerol (PG), and cardiolipin (CL), were distributed in highly asymmetric fashion; 95%–97% of LPG was associated with the inner leaflet whereas PG (~90%) and CL (~80%) were found predominantly in the outer leaflet. ECg elicited small, significant changes in LPG distribution. Atomic force microscopy established that ECg-exposed cells divided in similar fashion to control bacteria, with a thickened band of encircling peptidoglycan representing the most recent plane of cell division, less distinct ribs indicative of previous sites of orthogonal division and concentric rings and “knobbles” representing stages of peptidoglycan remodelling during the cell cycle. Preservation of staphylococcal membrane lipid asymmetry and mode of division in sequential orthogonal planes appear key features of ECg-induced stress.
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surfactant free purification of membrane protein complexes from bacteria application to the staphylococcal penicillin binding protein complex pbp2 pbp2a
Nanotechnology, 2014Co-Authors: Sarah Paulin, Helena Rosado, Simon J Foster, Mohammed Jamshad, Timothy R Dafforn, Jorge Garcialara, Nicola F Galley, David I Roper, Peter W TaylorAbstract:Surfactant-mediated removal of proteins from biomembranes invariably results in partial or complete loss of function and disassembly of multi-protein complexes. We determined the capacity of styrene-co-maleic acid (SMA) co-polymer to remove components of the cell division machinery from the membrane of drug-resistant staphylococcal cells. SMA-lipid nanoparticles solubilized FtsZ-PBP2-PBP2a complexes from intact cells, demonstrating the close physical proximity of these proteins within the lipid bilayer. Exposure of bacteria to (-)-Epicatechin Gallate, a polyphenolic agent that abolishes β-lactam resistance in staphylococci, disrupted the association between PBP2 and PBP2a. Thus, SMA purification provides a means to remove native integral membrane protein assemblages with minimal physical disruption and shows promise as a tool for the interrogation of molecular aspects of bacterial membrane protein structure and function.
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improved synthesis of structural analogues of Epicatechin Gallate for modulation of staphylococcal β lactam resistance
Tetrahedron, 2014Co-Authors: James C Anderson, Helen Grounds, Suzanna Reeves, Peter W TaylorAbstract:The high-yielding synthesis of enantiomerically pure Epicatechin Gallate analogues where the A and/or B-ring hydroxylation is reduced or altered has been achieved by optimising routes to the catechin stereochemistry. The B-ring analogues were synthesised by using an electrophilic ring closure onto an enantiomerically enriched epoxide as a key step. The A and B-ring hydroxyl-deleted analogues were synthesised through a Mitsunobu cyclisation. For the B-ring analogues, the anti- (catechin) stereochemistry was converted to the syn- (Epicatechin) stereochemistry by a known oxidation/reduction protocol. Absolute stereochemistry was derived from either a Sharpless epoxidation or asymmetric dihydroxylation.
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anti staphylococcal activity and β lactam resistance attenuating capacity of structural analogues of Epicatechin Gallate
Bioorganic & Medicinal Chemistry Letters, 2011Co-Authors: James C Anderson, Robert A Mccarthy, Sarah Paulin, Peter W TaylorAbstract:We examined the impact of gradual removal of hydroxyl groups from the A- and B-rings of (-)-Epicatechin Gallate on antibacterial activity and oxacillin resistance attenuation of an epidemic strain of methicillin resistant Staphylococcus aureus. Removal of both hydroxyls from the B-ring effected a large reduction in oxacillin MIC (from 512 to 0.25 mg/mL at a concentration of 12.5 mg/L); further hydroxyl deletion of the A-ring reduced the oxacillin effect but increased intrinsic anti-staphylococcal activity (C) 2011 Elsevier Ltd. All rights reserved.
Patricia Bernal - One of the best experts on this subject based on the ideXlab platform.
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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, 2010Co-Authors: Patricia Bernal, Sandrine Lemaire, Mariana G Pinho, Shahriar Mobashery, Jason Hinds, Peter W TaylorAbstract: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.
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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, 2010Co-Authors: Patricia Bernal, Sandrine Lemaire, Mariana G Pinho, Shahriar Mobashery, Jason Hinds, Peter W TaylorAbstract:Epicatechin Gallate (ECg) sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin and other β-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.
Jason Hinds - One of the best experts on this subject based on the ideXlab platform.
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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, 2010Co-Authors: Patricia Bernal, Sandrine Lemaire, Mariana G Pinho, Shahriar Mobashery, Jason Hinds, Peter W TaylorAbstract: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.
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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, 2010Co-Authors: Patricia Bernal, Sandrine Lemaire, Mariana G Pinho, Shahriar Mobashery, Jason Hinds, Peter W TaylorAbstract:Epicatechin Gallate (ECg) sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin and other β-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.
Mariana G Pinho - One of the best experts on this subject based on the ideXlab platform.
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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, 2010Co-Authors: Patricia Bernal, Sandrine Lemaire, Mariana G Pinho, Shahriar Mobashery, Jason Hinds, Peter W TaylorAbstract: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.
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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, 2010Co-Authors: Patricia Bernal, Sandrine Lemaire, Mariana G Pinho, Shahriar Mobashery, Jason Hinds, Peter W TaylorAbstract:Epicatechin Gallate (ECg) sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin and other β-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.
Shahriar Mobashery - One of the best experts on this subject based on the ideXlab platform.
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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, 2010Co-Authors: Patricia Bernal, Sandrine Lemaire, Mariana G Pinho, Shahriar Mobashery, Jason Hinds, Peter W TaylorAbstract: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.
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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, 2010Co-Authors: Patricia Bernal, Sandrine Lemaire, Mariana G Pinho, Shahriar Mobashery, Jason Hinds, Peter W TaylorAbstract:Epicatechin Gallate (ECg) sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin and other β-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.