Human amylin is a potent antimicrobial peptide that exhibits antimicrobial synergism with the amyloid beta protein.

INTRODUCTION: Our previous studies demonstrated the antimicrobial properties of amyloid beta (Aβ) of Alzheimer's disease (AD) against clinically relevant bacteria, yeast, and viruses. In this study, we investigate the antimicrobial function of the 37-amino acid amylin of type 2 diabetes (T2D), expanding on its potential involvement in AD. METHODS: We used in vitro assays, including human three-dimensional neuronal cell culture models, to test microbicidal, microbiostatic, and synergistic antimicrobial interactions between amylin and Aβ against microbes. RESULTS: Our results confirm that amylin is a broad-spectrum antimicrobial peptide that exhibits both microbicidal and microbiostatic mechanisms. We also identified a synergistic antimicrobial effect between amylin and Aβ in inhibiting Salmonella Typhimurium and Staphylococcus aureus. DISCUSSION: The findings show that amylin is an antimicrobial peptide and functions synergistically with Aβ against bacterial pathogens. Increased amylin secretion after bacterial infection suggests a broader biological role for amylin beyond its involvement in T2D. HIGHLIGHTS: Amylin is a potent antimicrobial peptide, eliminating ≥99.9% bacteria at low doses. Amylin efficiently traps and neutralizes microbes via a fibril-driven mechanism. Amylin protects human cells and Caenorhabditis elegans from Salmonella or Candida infection. Synthetic amylin and amyloid beta (Aβ) together amplify antibacterial response against bacteria. Synergy between cell-derived amylin and Aβ drives dynamic antimicrobial activity against neural infection.