Model membrane approaches to determine the role of calcium for the antimicrobial activity of friulimicin

Reder-Christ, Katrin and Falkenstein-Paul, Hildegard and Klocek, Gabriela and Al-Kaddah, Saad and Bakowsky, Udo and Bendas, Gerd. (2011) Model membrane approaches to determine the role of calcium for the antimicrobial activity of friulimicin. International Journal of Antimicrobial Agents , 37 (3). pp. 256-260.

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Official URL: http://edoc.unibas.ch/49529/

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Friulimicin is a cyclic lipopeptide antibiotic, currently in clinical development, that possesses excellent activity against Gram-positive bacteria, including multiresistant strains. A recent study on the mode of action of friulimicin reported on the interference with bacterial cell wall biosynthesis via a calcium-dependent complexing of the bactoprenol phosphate carrier C₅₅-P. The calcium dependency of this non-common targeted activity remains to be elucidated. In the present model membrane approach, the role of calcium for friulimicin targeting to C₅₅-P was investigated by biosensor-based detection of binding affinities. The findings were supplemented by atomic force microscopy (AFM) and circular dichroism (CD) spectroscopy. Comparing the calcium salt of friulimicin with the calcium-free peptide, calcium appeared to be essential for friulimicin interaction with DOPC model membranes. The binding affinity was even higher in the presence of 0.1 mol% C₅₅-P (0.21 μM vs. 1.22 μM), confirming the targeted mode of action. Binding experiments with supplemented calcium salts suggest (i) the phosphate group as the essential moiety of C₅₅-P, referring to a bridging function of calcium between the negatively charged friulimicin and C₅₅-P, and (ii) a structural effect of calcium shifting the peptide into a suitable binding conformation (CD spectra). AFM images confirmed that calcium has no, or only a minor, effect on the aggregate formation of friulimicin. These data shed new light on the mechanisms of antibacterial activity of friulimicin.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig J)
UniBasel Contributors:Québatte, Gabriela
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Nov 2017 07:34
Deposited On:30 Nov 2017 07:34

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