In vitro and in silico Evaluation of the Anti-Biofilm Activity of Histatin 5 against Streptococcus mutans

Dental caries is a prevalent and costly disease throughout the world. Streptococcus mutans is widely recognized as one of the key contributing factors in the development of dental caries. Major virulence factors associated with the cariogenicity of S. mutans include adhesion, formation biofilm, acidogenicity and acidurity. Histatin 5, a salivary antimicrobial peptide, exhibited therapeutic effects in the oral cavity. The aim of this study was to evaluate the potential anti-biofilm effects of histatin 5 against S. mutans via in vitro and in silico approaches. Also, the impact of histatin 5 on acidogenicity and acidurity was accessed. The resazurin microdilution method was used to evaluate the anti-biofilm and anti-adhesive activity. Furthermore, molecular docking was carried out to identify the crucial structural features of histatin 5 in binding to glucansucrase enzyme of S. mutans, which is involved in biofilm formation. The findings showed that histatin 5 considerably inhibited the biofilm formation of S. mutans in a dose-dependent manner and could potentially limit the acidogenicity and acidurity of S. mutans. The results of confocal laser scanning microscopy indicated the inhibitory effects of histatin 5 on biofilm formation of S. mutans cells. Moreover, histatin 5 displayed a favorable interaction with glucansucrase, which suggests that it could potentially act as an inhibitor for this enzyme. These findings suggest that histatin 5 could be a promising candidate for the development of a new efficient therapeutic agent for the prevention and treatment of dental caries.