Selective antibacterial activity of a novel lactotransferrin-derived antimicrobial peptide LF-1 against Streptococcus mutans

Streptococcus mutans is a key pathogen involved in the development of caries lesions. Previously, we developed a novel lactotransferrin-derived antimicrobial peptide LF-1 with potential selective activity against S. mutans. This study aimed to further confirm the selectivity of LF-1 by investigating its effect on S. mutans membrane.The effects of LF-1 on the viability of human gingival fibroblasts (HGFs) and three common oral Streptococcus (S. mutans, S. sanguinis, and S. gordonii) were evaluated and its structural characteristics were analysed using eukaryotic and prokaryotic membrane-simulated liposomes. Membrane affinity of LF-1 to the three streptococci strains was evaluated using the 3',3'-dipropylthiadicarbocyanine iodide experiment, hydrophobicity assay, and flow cytometry analysis. Transmission electron microscopy (TEM) was used to observe morphological changes in the three streptococcal membranes after LF-1 treatment.LF-1 displayed lower cytotoxicity to HGFs and selective antibacterial activity against S. mutans. LF-1 exhibited a typical α-helix structure and showed a tryptophan fluorescence blue shift in the prokaryotic membrane-simulated model. The most notable LF-1 induced changes occurred in the membrane potential and hydrophobicity of S. mutans among the three streptococci strains. Furthermore, the fluorescence of fluorescein isothiocyanate-labelled LF-1 was higher in S. mutans than in the other species. TEM showed that 16 μmol/L LF-1 could induce mesosome-like structures in S. mutans, whereas no significant morphological changes occurred in the other species.LF-1 has selective affinity for and antibacterial activity against S. mutans with strong membrane disrupting ability, highlighting the potential of LF-1 as a crucial antibacterial agent in caries prevention.