Screening of Streptococcus mutans Sortase A Via Myricetin-Like Inhibitors: In Vitro Evaluation and Molecular Docking- Based Virtual

Background: Dental caries is one of the most common causes threatening human health globally. Sortase A (Srt A) as a transpeptidase, mediates the attachment of the Streptococcus mutans cell wall to dental surfaces by biofilm formation. Due to the development of multidrug-resistance bacteria, attempting to discover growth inhibitors is logical and promising. Objectives: The current study aimed at the experimental and docking-based virtual screening of myricetinlike inhibitors for the inhibition of Srt A enzyme in S. mutans isolates. Methods: Sixty-three S. mutans were isolated from pupils based on cultural, morphological, and biochemical characteristics (N = ۱۵۰). After identifying the srtA gene using the polymerase chain reaction (PCR) with specific primers, a broth microdilution test was conducted according to CLSI-۲۰۲۰ criteria to determine the minimum inhibitory concentration (MIC) of myricetin. The in silico exploration of Srt A inhibitors was performed using AutoDock ۴.۲.۶. Results: The frequency of S. mutans isolates containing the srtA gene was ۸۷.۳% of which, fifty isolates (۷۹.۴%) were categorized as susceptible to myricetin (MIC ≤ ۱۶ μg/mL). Of ۲۰ ligands having a high degree of similarity with myricetin, the best docking results were related to ligand ۲. Conclusion: It was concluded that myricetin has an inhibitory effect on oral bacteria in vitro, and ligand ۲ had the most negative binding energy (-۴.۶۶ kcal/mol) and favorably interacts with the key amino acid residues at the active site of Srt A. Accordingly, this ligand can be utilized as a lead compound for further studies to discover novel inhibitors targeting Srt A in S. mutans.

Keywords:

Streptococcus mutans , Molecular docking , Myricetin , Sortase A