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.
authors.affiliation: Laboratory of Analytical Chemistry, Department of Chemistry, 00014 University of Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Muhonen
authors.forename: Jukka
authors.initials: J
authors.lastname: Vidgren
authors.forename: Anne
authors.initials: A
authors.lastname: Helle
authors.forename: Gebrenegus
authors.initials: G
authors.lastname: Yohannes
authors.forename: Tapani
authors.initials: T
authors.lastname: Viitala
authors.forename: Juha M
authors.initials: JM
authors.lastname: Holopainen
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Wiedmer
mesh_terms: D053801:Capillary Electrochromatography; D002784:Cholesterol / Q000737:chemistry*; D053841:Electroosmosis; D005672:Fusidic Acid / Q000737:chemistry*; D008081:Liposomes; D008567:Membranes, Artificial; D020653:Peptide Elongation Factor G / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*
chemical_list: D008081:Liposomes; D008567:Membranes, Artificial; D020653:Peptide Elongation Factor G; D010713:Phosphatidylcholines; D005672:Fusidic Acid; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine