Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements

Saad Al-Kaddah (1) , Katrin Reder-Christ (1) , Gabriela Klocek (2) , Imke Wiedemann (3) , Manuela Brunschweiger (1) , Gerd Bendas (1)

1 Department of Pharmacy
2 Department of Biophysical Chemistry
3 Institute of Medical Microbiology

The interaction of the lantibiotic gallidermin and the glycopeptide antibiotic vancomycin with bacterial membranes was simulated using mass sensitive biosensors and isothermal titration calorimetry (ITC). Both peptides interfere with cell wall biosynthesis by targeting the cell wall precursor lipid II, but differ clearly in their antibiotic activity against individual bacterial strains. We determined binding affinities of vancomycin and gallidermin to model membranes±lipid II in detail. Both peptides bind to DOPC/lipid II membranes with high affinity (K 0.30μM and 0.27μM). Gallidermin displayed also strong affinity to pure DOPC membranes (0.53μM) an effect that was supported by ITC measurements. A surface acoustic wave (SAW) sensor allowed measurements in the picomolar concentration range and revealed that gallidermin targets lipid II at an equimolar ratio and simultaneously inserts into the bilayer. These results indicate that gallidermin, in contrast to vancomycin, combines cell wall inhibiton and interference with the bacterial membrane integrity for potent antimicrobial activity.

Mots clés: MC 540; MIC; QCM; SAW; Antibiotics; Gallidermin; Isothermal Titration Calorimetry (ITC); Lipid II; Surface Acoustic Wave (SAW) biosensor; Vancomycin; AMPs; DOPC; DOPG; ITC

Domaines: Chimie-Physique [physics.chem-ph]

Saad Al-Kaddah, Katrin Reder-Christ, Gabriela Klocek, Imke Wiedemann, Manuela Brunschweiger, et al.. Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements. Biophysical Chemistry, 2010, 152 (1-3), pp.145. ⟨10.1016/j.bpc.2010.09.002⟩. ⟨hal-00694292⟩