Interactions of fusidic acid and elongation factor G with lipid membranes

Jaana Muhonen; Jukka Vidgren; Anne Helle; Gebrenegus Yohannes; Tapani Viitala; Juha M. Holopainen; Susanne K. Wiedmer

doi:10.1016/j.ab.2007.10.014

Interactions of fusidic acid and elongation factor G with lipid membranes

Jaana Muhonen, Jukka Vidgren, Anne Helle, Gebrenegus Yohannes, Tapani Viitala, Juha M. Holopainen^*, Susanne K. Wiedmer

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

19 Citations (Scopus)

Abstract

Fusidic acid (FA) is a potent antibiotic and blocks the protein synthesis by binding to elongation factor G (EF-G) directly. Here we hypothesized that the antibiotic activity of FA would be potentiated by several orders of magnitude if both FA and EF-G would be residing in the lipid membranes and, hence, the probability of interaction would transform from three-dimensional to two-dimensional. Such detailed information could lead to more effective therapeutic interventions if they are understood on a molecular level. Interactions between FA and various lipid membranes composed of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and cholesterol (Chol) were studied by capillary electrochromatography (CEC). The influence of the lipid vesicle size-sonicated liposomes and liposomes extruded through 30-, 50-, and 100-nm filters-on the packing of vesicles on the silica capillary surface was investigated by CEC and dissipative quartz crystal microbalance. The CEC results evidenced that FA interacts with and resides in phospholipid membranes. Likewise, monolayer, asymmetrical flow field flow fractionation, and CEC studies confirmed that EF-G is hydrophobic and incorporated into POPC and POPC/Chol membranes. Including EF-G in phospholipid vesicles did not improve the binding of FA to the membranes.

Original language	English
Pages (from-to)	133-142
Number of pages	10
Journal	Analytical Biochemistry
Volume	374
Issue number	1
DOIs	https://doi.org/10.1016/j.ab.2007.10.014
Publication status	Published - 1 Mar 2008
Externally published	Yes
MoE publication type	A1 Journal article-refereed

Funding

Financial support was received from the Academy of Finland (SA 202216, 114292) (SKW) and Sigrid Juselius Foundation, The Helsinki University Central Hospital Research Fund, and Evald and Hilda Nissi Foundation (JMH). The authors thank Dr. Jari Metso (Department of Molecular Medicine, National Public Health Institute, Helsinki) for help with the radioactivity measurements. The donation of EF-G by Dr. Suparna Sanyal (Department of Cell and Molecular Biology, Uppsala University, Sweden) is much appreciated.

Keywords

Capillary electromigration techniques
Elongation factor G
Field flow fractionation
Fusidic acid
Liposomes
Quartz crystal microbalance

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10.1016/j.ab.2007.10.014

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title = "Interactions of fusidic acid and elongation factor G with lipid membranes",

abstract = "Fusidic acid (FA) is a potent antibiotic and blocks the protein synthesis by binding to elongation factor G (EF-G) directly. Here we hypothesized that the antibiotic activity of FA would be potentiated by several orders of magnitude if both FA and EF-G would be residing in the lipid membranes and, hence, the probability of interaction would transform from three-dimensional to two-dimensional. Such detailed information could lead to more effective therapeutic interventions if they are understood on a molecular level. Interactions between FA and various lipid membranes composed of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and cholesterol (Chol) were studied by capillary electrochromatography (CEC). The influence of the lipid vesicle size-sonicated liposomes and liposomes extruded through 30-, 50-, and 100-nm filters-on the packing of vesicles on the silica capillary surface was investigated by CEC and dissipative quartz crystal microbalance. The CEC results evidenced that FA interacts with and resides in phospholipid membranes. Likewise, monolayer, asymmetrical flow field flow fractionation, and CEC studies confirmed that EF-G is hydrophobic and incorporated into POPC and POPC/Chol membranes. Including EF-G in phospholipid vesicles did not improve the binding of FA to the membranes.",

keywords = "Capillary electromigration techniques, Elongation factor G, Field flow fractionation, Fusidic acid, Liposomes, Quartz crystal microbalance",

author = "Jaana Muhonen and Jukka Vidgren and Anne Helle and Gebrenegus Yohannes and Tapani Viitala and Holopainen, \{Juha M.\} and Wiedmer, \{Susanne K.\}",

note = "Funding Information: Financial support was received from the Academy of Finland (SA 202216, 114292) (SKW) and Sigrid Juselius Foundation, The Helsinki University Central Hospital Research Fund, and Evald and Hilda Nissi Foundation (JMH). The authors thank Dr. Jari Metso (Department of Molecular Medicine, National Public Health Institute, Helsinki) for help with the radioactivity measurements. The donation of EF-G by Dr. Suparna Sanyal (Department of Cell and Molecular Biology, Uppsala University, Sweden) is much appreciated.",

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doi = "10.1016/j.ab.2007.10.014",

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AU - Muhonen, Jaana

AU - Vidgren, Jukka

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AU - Yohannes, Gebrenegus

AU - Viitala, Tapani

AU - Holopainen, Juha M.

AU - Wiedmer, Susanne K.

N1 - Funding Information: Financial support was received from the Academy of Finland (SA 202216, 114292) (SKW) and Sigrid Juselius Foundation, The Helsinki University Central Hospital Research Fund, and Evald and Hilda Nissi Foundation (JMH). The authors thank Dr. Jari Metso (Department of Molecular Medicine, National Public Health Institute, Helsinki) for help with the radioactivity measurements. The donation of EF-G by Dr. Suparna Sanyal (Department of Cell and Molecular Biology, Uppsala University, Sweden) is much appreciated.

PY - 2008/3/1

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N2 - Fusidic acid (FA) is a potent antibiotic and blocks the protein synthesis by binding to elongation factor G (EF-G) directly. Here we hypothesized that the antibiotic activity of FA would be potentiated by several orders of magnitude if both FA and EF-G would be residing in the lipid membranes and, hence, the probability of interaction would transform from three-dimensional to two-dimensional. Such detailed information could lead to more effective therapeutic interventions if they are understood on a molecular level. Interactions between FA and various lipid membranes composed of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and cholesterol (Chol) were studied by capillary electrochromatography (CEC). The influence of the lipid vesicle size-sonicated liposomes and liposomes extruded through 30-, 50-, and 100-nm filters-on the packing of vesicles on the silica capillary surface was investigated by CEC and dissipative quartz crystal microbalance. The CEC results evidenced that FA interacts with and resides in phospholipid membranes. Likewise, monolayer, asymmetrical flow field flow fractionation, and CEC studies confirmed that EF-G is hydrophobic and incorporated into POPC and POPC/Chol membranes. Including EF-G in phospholipid vesicles did not improve the binding of FA to the membranes.

AB - Fusidic acid (FA) is a potent antibiotic and blocks the protein synthesis by binding to elongation factor G (EF-G) directly. Here we hypothesized that the antibiotic activity of FA would be potentiated by several orders of magnitude if both FA and EF-G would be residing in the lipid membranes and, hence, the probability of interaction would transform from three-dimensional to two-dimensional. Such detailed information could lead to more effective therapeutic interventions if they are understood on a molecular level. Interactions between FA and various lipid membranes composed of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and cholesterol (Chol) were studied by capillary electrochromatography (CEC). The influence of the lipid vesicle size-sonicated liposomes and liposomes extruded through 30-, 50-, and 100-nm filters-on the packing of vesicles on the silica capillary surface was investigated by CEC and dissipative quartz crystal microbalance. The CEC results evidenced that FA interacts with and resides in phospholipid membranes. Likewise, monolayer, asymmetrical flow field flow fractionation, and CEC studies confirmed that EF-G is hydrophobic and incorporated into POPC and POPC/Chol membranes. Including EF-G in phospholipid vesicles did not improve the binding of FA to the membranes.

KW - Capillary electromigration techniques

KW - Elongation factor G

KW - Field flow fractionation

KW - Fusidic acid

KW - Liposomes

KW - Quartz crystal microbalance

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DO - 10.1016/j.ab.2007.10.014

M3 - Article

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AN - SCOPUS:38649137725

SN - 0003-2697

VL - 374

SP - 133

EP - 142

JO - Analytical Biochemistry

JF - Analytical Biochemistry

IS - 1

ER -

Interactions of fusidic acid and elongation factor G with lipid membranes

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