Battacin-inspired Ultrashort Peptides: Nanostructure Analysis and Antimicrobial Activity

Peptides can serve as versatile therapeutics with a highly modular structure and tunable biophysical properties. In particular, the efficacy of peptide antibiotics against drug-resistant pathogens is of great promise, as few new classes of antibiotics are being developed to overcome the ever-increasing bacterial resistance to contemporary drugs. This work reports biophysical and antimicrobial studies of a designed library of ultrashort peptides that self-assemble into hydrogels at concentrations as low as 0.5% w/v in buffered saline, as confirmed by rheology. The hydrogels are constituted by β-sheet-rich nanofibril networks, as determined by biophysical techniques including spectroscopy (attenuated total reflectance Fourier transform infrared spectroscopy and Congo red binding assay), short- and wide-angle X-ray scattering, and electron microscopy. Both peptide solutions and self-assembled hydrogels show potent antimicrobial activity against S. aureus and Pseudomonas aeruginosa by membrane lysis. These pe...