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

Abstract

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=150). After identifying the srtA gene using the polymerase chain reaction (PCR) with specific primers, a broth microdilution test was conducted according to CLSI-2020 criteria to determine the minimum inhibitory concentration (MIC) of myricetin. The in silico exploration of Srt A inhibitors was performed using AutoDock 4.2.6. Results: The frequency of S. mutans isolates containing the srtA gene was 87.3% of which, fifty isolates (79.4%) were categorized as susceptible to myricetin (MIC,≤16 μg/mL). Of 20 ligands having a high degree of similarity with myricetin, the best docking results were related to ligand 2. Conclusion: It was concluded that myricetin has an inhibitory effect on oral bacteria in vitro, and ligand 2 had the most negative binding energy (-4.66 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.