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Membrane topology of a broad-spectrum resistance factor responsible for lipid modification in Enterococcus faecium.

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Date Issued:
2015
Abstract/Description:
Aminoacylphosphatidylglycerol synthases (aaPGSs) are integral membrane proteins that use aminoacyl-tRNAs as substrates to catalyze the addition of amino acids to phosphatidylglycerol (PG) in the cytoplasmic membranes of bacteria. Addition of amino acids to PG decreases the net negative charge of the membrane, conferring resistance to various classes of antibacterial agents (i.e., cationic antimicrobial peptides, beta-lactams, glycopeptides, and lipopeptides) and protecting the cell against osmotic stress and acidic conditions. aaPGS homologs are found in a variety of clinically relevant microorganisms, including Enterococcus faecium, which is increasingly found to be the etiologic agent of antibiotic-resistant nosocomial infections. Although the broad distribution of these virulence factors across bacterial species makes them attractive targets for therapeutic strategies, little is known about the structure of aaPGSs. Two aaPGS paralogs are found in E. faecium, one of which exhibits relaxed substrate specificity and is responsible for the transfer of Arg (R), Ala (A), and Lys (K) to PG (RakPGS). The catalytic site of RakPGS is located in the hydrophilic C-terminal domain, which is localized in the cytoplasm. The N-terminus contains an integral membrane domain that is thought to harbor flippase activity that translocates the neosynthesized aa-PG from the inner to the outer leaflet of the membrane. We are currently developing the substituted cysteine accessibility method (SCAM) and a dual-reporter fusion system, which exploits alkaline phosphatase (Pho) and ?-galactosidase (LacZ) activities, for investigating the membrane topology of RakPGS in E. faecium.
Title: Membrane topology of a broad-spectrum resistance factor responsible for lipid modification in Enterococcus faecium.
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Name(s): Harrison, Jesse, Author
Roy, Herve, Committee Chair
Teter, Kenneth, Committee Member
Phanstiel, Otto, Committee Member
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2015
Publisher: University of Central Florida
Language(s): English
Abstract/Description: Aminoacylphosphatidylglycerol synthases (aaPGSs) are integral membrane proteins that use aminoacyl-tRNAs as substrates to catalyze the addition of amino acids to phosphatidylglycerol (PG) in the cytoplasmic membranes of bacteria. Addition of amino acids to PG decreases the net negative charge of the membrane, conferring resistance to various classes of antibacterial agents (i.e., cationic antimicrobial peptides, beta-lactams, glycopeptides, and lipopeptides) and protecting the cell against osmotic stress and acidic conditions. aaPGS homologs are found in a variety of clinically relevant microorganisms, including Enterococcus faecium, which is increasingly found to be the etiologic agent of antibiotic-resistant nosocomial infections. Although the broad distribution of these virulence factors across bacterial species makes them attractive targets for therapeutic strategies, little is known about the structure of aaPGSs. Two aaPGS paralogs are found in E. faecium, one of which exhibits relaxed substrate specificity and is responsible for the transfer of Arg (R), Ala (A), and Lys (K) to PG (RakPGS). The catalytic site of RakPGS is located in the hydrophilic C-terminal domain, which is localized in the cytoplasm. The N-terminus contains an integral membrane domain that is thought to harbor flippase activity that translocates the neosynthesized aa-PG from the inner to the outer leaflet of the membrane. We are currently developing the substituted cysteine accessibility method (SCAM) and a dual-reporter fusion system, which exploits alkaline phosphatase (Pho) and ?-galactosidase (LacZ) activities, for investigating the membrane topology of RakPGS in E. faecium.
Identifier: CFE0006318 (IID), ucf:51566 (fedora)
Note(s): 2015-12-01
M.S.
Medicine, Molecular Biology and Micro
Masters
This record was generated from author submitted information.
Subject(s): phosphatidylglycerol -- membrane topology -- cationic antimicrobial peptides -- aaPGS -- membrane lipids
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFE0006318
Restrictions on Access: campus 2021-06-15
Host Institution: UCF

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