RATIONAL DESIGN OF PEPTIDE NANONETS FOR ANTIBACTERIAL TRAP-AND-KILL

Abstract

In nature, bacteria-trapping nanonets are increasingly recognized as a prominent immune defense strategy against infectious bacteria. The overarching objective of this thesis was to develop synthetic peptide nanonets for antibacterial trap-and-kill. From a de novo designed library of antimicrobial β-hairpin peptides, BTT2 was microscopically visualized to generate bacteria-trapping nanonets, based on which we developed a series of bacteria-responsive peptide nanonets. Peptide properties were demonstrated to be tunable through sequence manipulation. For modulating the dimensions of the nanonets, we employed short non-amyloidogenic peptides which inhibited fibril elongation. Although the addition of amyloid modulators induced a significant decrease in nanofibril length, it did not translate to a compromise in their trapping and killing efficacy. In summary, the research findings presented in this thesis highlight the anti-infective potentials of synthetic peptide nanonets and contribute to advance their development to tackle the antibiotic resistance crisis.