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 journalArticleScientificpeer-review

17 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 languageEnglish
Pages (from-to)133-142
Number of pages10
JournalAnalytical Biochemistry
Volume374
Issue number1
DOIs
Publication statusPublished - 1 Mar 2008
Externally publishedYes
MoE publication typeA1 Journal article-refereed

Keywords

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

Fingerprint

Dive into the research topics of 'Interactions of fusidic acid and elongation factor G with lipid membranes'. Together they form a unique fingerprint.

Cite this