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Shahar Rotem

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  1. 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

  2. Antibiotic resistance

  3. What are AntiMicrobial Peptides (AMPs) ? • Widely distributed in nature, host defensemolecules.

  4. What are AntiMicrobial Peptides (AMPs) ? • Widely distributed in nature, host defensemolecules. • Net positive charge, relatively high hydrophobicity, amphipathic. • Challenge resistancemechanisms.

  5. 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

  6. Mechanism of action

  7. Membrane Architecture and Energy Charge Membrane composition Trans-membrane potential -90 -110 mV -130 -150 mV

  8. AFM E.coli after incubation in presence of AMP E.coli control Li et al (BBA 2007)

  9. AMP advantages: 1. molecular simplicity 2. large spectrum of activity 3. challenge in resistance development

  10. AMP Bactericidal kinetics against E. coliat 6 x MIC

  11. AMP Evolution of MICs on E. coli after 15 serial passages. Resistance studies

  12. Peptides and peptidomimetics in commercial development Hancock RE, Sahl HG. NBT 2006

  13. 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

  14. Dermaseptin (1-16) (fatty acid-Lysine)n

  15. 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