DEVELOPMENT OF NOVEL ANTIMICROBIAL SELF-ASSEMBLING NANO-STRUCTURES

Lee Schnaider ¹ Sayanti Brahmachari ¹ William F. DeGrado ^3,4 Ehud Gazit ^1,2

¹Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
²Department of Materials Science and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel
³Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA
⁴Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA

The development of novel antimicrobial therapy is a significant challenge for the 21^st century with more deaths currently resulting from methicillin-resistant S. aureus (MRSA) infections than from HIV. Antibiotic resistance is a life-threatening phenomenon as well as a substantial economic burden to the global public. Thus, antibacterial agents directed towards new physiological targets with a reduced tendency for the emergence of resistance are highly needed.

Antimicrobial peptides, originally identified as mediators of innate immunity in various organisms and later synthetically designed and produced, were previously envisioned as a viable alternative to classical antibiotics. Yet, their relatively large size and pronounced side effects limit their clinical utilization. A recent extension to the mechanistic understanding of antimicrobial peptide activity came from the discovery of the common properties they share with amyloid assemblies. Through our reductionist methodology, we have developed a new class of antimicrobial nano-structures. These are based on our identification of the shortest building-blocks which form amyloid-like assemblies with antimicrobial capabilities. The newly designed agents are based on significantly smaller peptides than those previously utilized. We have already provided a proof of concept for this approach through our identification of significant antimicrobial activity of nanostructures formed by the self-association of ultra-short peptides. Furthermore, we have successfully incorporated these nanostructures in biocompatible films which provided them with antibacterial functionality and are designing additional functional antimicrobial biomaterials.

This interdisciplinary approach combines the two distinct fields of microbiology and peptide self-assembly which are not classically thought to have common ground but initial results reveal the significance of the interplay between them. We believe our antimicrobial self-assembling nano-structures should provide a new horizon for the development of improved antimicrobial therapies.