Antimicrobial peptides derived from human ameloblastin targeting biofilms

Oral biofilm-related diseases, such as dental caries and periodontitis, remain among the most prevalent global health issues and are increasingly complicated by antibiotic resistance and biofilm persistence, which limit the effectiveness of conventional treatments. This study addresses the challenges by exploring antimicrobial peptides (AMPs) derived from ameloblastin (AMBN), a protein integral to dental biomineralization and categorized as an intrinsically disordered protein. In humans, the AMBN gene encodes two isoforms, ISO I and ISO II, with distinct but not fully understood functions. Four AMBN ISO I-derived peptides (A, Am, B, Bm) were designed, synthesized, and tested for antimicrobial and antibiofilm activity. Peptides A and Am moderately inhibited biofilms of E. faecalis, S. aureus, and E. coli (MBIC₅₀ within 50-300 µM), including resistant isolates, while B and Bm were more effective against Gram-positive strains, showing the strongest effect against methicillin-resistant S. aureus CNCTC 6271. Cytotoxicity assays showed > 90% cell viability at 50 µM and IC₅₀ >100 µM for HCT116 and > 300 µM for HUVEC cells, with haemolytic activity > 300 µM. Stable immobilization of peptides on titanium surfaces was confirmed by XPS and QCM-D techniques, supporting their potential as low-toxicity antimicrobial coatings for medical implants.