An Ultrastable Self‐Assembled Antibacterial Nanospears Made of Protein

Protein-based nanomaterials have broad applications in the biomedical and bionanotechnological sectors owing to their outstanding properties such as high biocompatibility and biodegradability, structural stability, sophisticated functional versatility, and being environmentally benign. They have gained considerable attention in drug delivery, cancer therapeutics, vaccines, immunotherapies, biosensing, and biocatalysis. However, so far, in the battle against the increasing reports of antibiotic resistance and emerging drug-resistant bacteria, unique nanostructures of this kind are lacking, hindering their potential next-generation antibacterial agents. Here, the discovery of a class of supramolecular nanostructures with well-defined shapes, geometries, or architectures (termed "protein nanospears") based on engineered proteins, exhibiting exceptional broad-spectrum antibacterial activities, is reported. The protein nanospears are engineered via spontaneous cleavage-dependent or precisely tunable self-assembly routes using mild metal salt-ions (Mg2+ , Ca2+ , Na+ ) as a molecular trigger. The nanospears' dimensions collectively range from entire nano- to micrometer scale. The protein nanospears display exceptional thermal and chemical stability yet rapidly disassemble upon exposure to high concentrations of chaotropes (>1 mm sodium dodecyl sulfate (SDS)). Using a combination of biological assays and electron microscopy imaging, it is revealed that the nanospears spontaneously induce rapid and irreparable damage to bacterial morphology via a unique action mechanism provided by their nanostructure and enzymatic action, a feat inaccessible to traditional antibiotics. These protein-based nanospears show promise as a potent tool to combat the growing threats of resistant bacteria, inspiring a new way to engineer other antibacterial protein nanomaterials with diverse structural and dimensional architectures and functional properties.