An Ultrastable Self‐Assembled Antibacterial Nanospears Made of Protein

Abstract

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 (Mg 2+ , Ca 2+ , 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.

Phage‐displayed heptapeptide sequence conjugation significantly improves the specific targeting ability of antimicrobial peptides against Staphylococcus aureus

“…The assay was performed to analyze the salt ion stability of SFK2 by measuring changes in MIC values in different physiological salt concentrations 38,46 . Different concentrations of salts (0.3 M NaCl, 9 × 10 −3 M KCl, 2×10 −3 M MgCl 2 , 1.6 × 10 −5 M ZnCl 2 , 1.2 × 10 −5 M NH 4 Cl, and 6 × 10 −6 M FeCl 3 ) were dissolved in BSA diluent, and the next steps were the same as those for the determination of MIC.…”

Toward Clinical Applications: Transforming Nonantibiotic Antibacterials into Effective Next-Generation Supramolecular Therapeutics

“…While these mechanisms continually evolve, antibiotic actions are probably preset and unvarying. When confronted with such a disparity between bacterial evolution and antibiotic development, researchers have shifted their focus toward alternative or innovative treatment solutions such as bacteriophage therapy, endolysins, − and antimicrobial peptides , coined herein as nonantibiotic antibacterials. These alternatives produce strong antibacterial effects via mechanism of actions (Figure D) and therefore demonstrate minimal impact on the likelihood of bacterial resistance evolving. ,, In addition, they have coexisted with microorganisms for millions of years without causing widespread resistance, strongly indicating that they are ideal candidates or substitutes for antibiotics and could prevent the emergence of drug resistance.…”

Size-dependent magnetomechanically enhanced photothermal antibacterial effect of Fe3O4@Au/PDA nanodurian

“…6–11 Unlike traditional antibiotics which were only capable of directly inhibiting specific bacterial metabolic processes, nanoplatforms can assume multiple functions concurrently, thereby mitigating the emergence of bacterial resistance. 12–20 Furthermore, a range of stimulus-activated nanoplatforms have been designed, using ultrasound, 21 microwave, 22 light 23–27 and magnetic fields 28–31 as sources of stimulation. These nanoplatforms have been programmed to remain dormant until they are required.…”