Technion – Israel Institute of Technology Faculty of Biotechnology and Food Eng. Antimicrobial peptides – A plausible replacement for antibiotics? Antimicrobial peptides – Overcoming bacterial resistance? Shahar Rotem
What are AntiMicrobial Peptides (AMPs) ? • Widely distributed in nature, host defensemolecules.
What are AntiMicrobial Peptides (AMPs) ? • Widely distributed in nature, host defensemolecules. • Net positive charge, relatively high hydrophobicity, amphipathic. • Challenge resistancemechanisms.
AMP features Charge Hydropho- bicity Conformation looped thanatin ß-sheeted polyphemusin Mixed structure of human ß-defensin-2 a-helical magainin-2 extended indolicidin rabbit kidney defensin-1
Membrane Architecture and Energy Charge Membrane composition Trans-membrane potential -90 -110 mV -130 -150 mV
AFM E.coli after incubation in presence of AMP E.coli control Li et al (BBA 2007)
AMP advantages: 1. molecular simplicity 2. large spectrum of activity 3. challenge in resistance development
AMP Bactericidal kinetics against E. coliat 6 x MIC
AMP Evolution of MICs on E. coli after 15 serial passages. Resistance studies
Peptides and peptidomimetics in commercial development Hancock RE, Sahl HG. NBT 2006
AMP advantages: 1. molecular simplicity 2. large spectrum of activity 3. challenge in resistance development AMP disadvantages: 1. toxicity 2. sensitivity to proteases 3. cost
Dermaseptin (1-16) (fatty acid-Lysine)n
Acknowledgments Prof. Amram Mor Fadia Zaknoon Shahar Rotem Tali Rydlo Keren Marinko Yaara Porat Viki Held-Kuznezov Lior Ziserman Dima Bourdetsky Hadar Feferovich Tchelet Kovachi Einat Karni