De Novo Design of a pH-triggered Self-assembled β-hairpin Nano Peptide for the Dual Biological Function of Antibacterial and Entrapment

Abstract

BackgroundAcid-tolerant enteric pathogens could evade small intestinal acid barriers, colonizing and infecting the intestinal tract. Whereas broad-spectrum antibiotics are not the best therapeutic strategy because of the disruption of intestinal flora caused by its indiscriminate antimicrobial activity against beneficial and harmful bacteria. So that is what inspired us to combine pH regulation with nanotechnology to develop a pH-triggered site-targeted antimicrobial peptide with entrapping function. ResultsAccording to the features of amino-acid building blocks and the diagonal cation–π interaction principle, a self-assembled peptide (SAP) was designed, and the results showed that changes in pH conditions could trigger the transformation of the microstructure of the nanopeptide, which has great antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Bacillus cereus under acidic conditions by disrupting bacterial membrane integrity, and great biocompatibility in vivo and in vitro and high tolerance. Moreover, SAP at high concentrations showed the entrapment property, which plays an important role in phagocytic clearance in the infection forces.ConclusionsOur study revealed the antibacterial activity of a short β-hairpin forming self-assembled peptide and establishes an innovative design strategy for peptide-based nanomaterials and a new treatment strategy for gastrointestinal bacterial infection.