Krill Prize Laureate 2018
New Structure-activity Paradigms for Amyloids from Pathogenic Microbes
Microbial functional amyloids form protein fibrils that serve as key virulence determinants and participate in aggressive infections. Yet, amyloids are mostly
known for their involvement in fatal neurodegenerative diseases and their structures have been studied mostly in eukaryotes. Our lab pioneered the investigations of bacterial functional amyloids at the atomic level, and published the first structure of an amyloid fibril from bacteria (Tayeb-Fligelman et. al., Science 2017). The structure
revealed a unique cross-α amyloid-like fibril which presented a paradigm shift in amyloid research, where it has been believed that β-rich structures are
central. The novel fibril structure is of PSMα3, a virulent peptide secreted by the pathogenic bacterium Staphylococcus aureus that is toxic to human cells.
Given this and other results we show that the structural and functional repertoire of microbial amyloids is far more diverse than previously anticipated, providing
a rich source of targets for antimicrobial drug discovery.