Novel lactotransferrin-derived synthetic peptides suppress cariogenic bacteria in vitro and arrest dental caries in vivo

ABSTRACT

Objectives: The aim of the study was to design and synthesise novel lactotransferrin-derived antimicrobial peptides (AMPs) with enhanced antibacterial activity against cariogenic bacteria.

Methods: We obtained the LF-1 (WKLLRKAWKLLRKA) and LF-2 (GKLIWKLLRKAWKLLRKA) AMPs, based on the N-terminal functional sequence of lactotransferrin, and characterised their physicochemical properties and secondary structure. Their antibacterial activity against caries-associated bacteria was evaluated using bacterial susceptibility and time-killing assays, as well as transmission electron microscopy (TEM). The antibiofilm activity against Streptococcus mutans biofilms was determined using biofilm susceptibility assays and confocal laser scanning microscopy (CLSM). A rodent model of dental caries was adopted to evaluate their anticaries effectiveness in vivo.

Results: Both peptides possessed an α-helical structure with excellent amphipathicity. LF-1 was effective against S. mutans and Actinomyces species, whereas LF-2 showed more potent antibacterial activity than LF-1 against a broader spectrum of tested strains. Both peptides inhibited the formation of S. mutans biofilm starting at 8 μmol/L and exerted effective eradication of S. mutans in preformed biofilms. Both peptides exhibited satisfactory biocompatibility and exerted significant anticaries effects in a rodent model.

Conclusions: Both lactotransferrin-derived peptides displayed strong antimicrobial activity against cariogenic bacteria and S. mutans biofilm in vitro and effectively inhibited dental caries in vivo.

KEYWORDS:

• Antimicrobial peptide
• biofilm
• dental caries
• lactotransferrin
• rat
• Streptococcus mutans

Acknowledgments

This study was funded by the National Natural Science Foundation of China [grant number: 81771062], and the peptide synthesis was supported by Zhejiang Ontores Biotechnologies Co., Ltd.

Disclosure of potential conflicts of interest

No potential conflict of interest was reported by the author(s).

Supplementary material

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Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81771062].