The present study aimed to design, synthesize and screen specifically targeted antimicrobial peptides (STAMPs) that can selectively kill Streptococcus mutans (S. mutans) in the biofilm, and to detect protein metabolism, in order to investigate the mechanism of the antibacterial functions of STAMPs against S. mutans. A series of STAMPs were synthesized, and their effects on the selective antibacterial activity of S. mutans on single species and multi-species biofilms under the condition of the planktonic state were studied. The total protein of S. mutans was extracted before and after C11H, and matrix-assisted laser adsorption ionization-time of flight mass spectrometry identification was performed. The antibacterial activity on planktonic S. mutans was increased 3- to 4-fold via C8H, C11H, C12H, C13H, and C14H compared with hLF1-11 (H) alone, and there was no difference between Streptococcus gordonii (S. gordonii) and Streptococcus sanguis (S. sanguis). C8H, C11H, C12H, C13H, and C14H had significant inhibitory effects on the growth of S. mutans biofilm, but there were no significant effects on S. gordonii and S. sanguis biofilms. The number of S. mutans in biofilm decreased at 4 h after C8H, C11H, C12H, C13H and C14H and C8, C11, C12, C13 and C14 had no effect on the growth of planktonic and biofilm states of S. mutans, S. gordonii and S. sanguis species. C11H and C12H exhibited the most obvious effects, followed by C13H and C14H, and then C8H. A total of 21 protein spots with a mean change ratio of 1.5 were identified, all of which were downregulated after C11H. A total of 19 proteins were successfully identified, including cell cycle‑relative proteins, nucleic acid metabolism-related enzymes and proteins, virulence factors, protein biosynthesis and regulation, proteins involved in energy metabolism, and proteins with unknown function. In the present study, STAMPs with selective antibacterial activity against S. mutans grown in planktonic or biofilm states but without obvious effects on oral Streptococci and multi-species biofilm were successfully designed and synthesized. Differential protein expression before and after C11H was identified. The mechanism of the antibacterial function was also discussed. Results of the present study laid the foundation for application of STAMPs in the prevention and treatment of dental caries.

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