Enhancement of hypericin nanoparticle-mediated sonoinduced disruption of biofilm and persister cells of Streptococcus mutans by dermcidin-derived peptide DCD-1L

•The amount of ROS produced by HypNP-DCD-1 L with the ultrasound waves increased 4.2-fold.•The combination of ultrasound waves with HypNP-DCD-1 L significantly degraded S. mutans biofilm by 5.1 log10 CFU/mL.•HypNP-DCD-1L-mediated aSDT can efficiently reduce the pathogenicity of S. mutans via downregulating the biofilm-associated genes.•aSDT using HypNP-DCD-1 L reduce the persistence phenotype by suppressing the expression of genes associated persister cells formation. Streptococcus mutans is considered a major significant contributor to dental caries and its effective removal is difficult due to the formation of biofilm. Therefore, the development of adjuvant therapeutic strategies with anti-biofilm properties is a promising approach. In the present study, we examined the effect of dermcidin-derived peptide DCD-1 L on the antibacterial activity of hypericin nanoparticle (HypNP)-mediated antimicrobial sonodynamic therapy (aSDT) against persister cells growing- and biofilm cultures of S. mutans. Following synthesis and confirmation of HypNP, the fractional inhibitory concentration (FIC) index of HypNP and DCD-1 L was determined by checkerboard assay. Cellular uptake of HypNP-DCD-1 L and generation of endogenous reactive oxygen species (ROS) were assessed and followed by the determination of antimicrobial sonoactivity of HypNP-DCD-1 L against persister cells growing- and biofilm cultures of S. mutans. The water-insoluble extracellular polysaccharide (EPS) and expression of the gtfD, comDE, and smuT genes were then evaluated in persister cells growing- and biofilm cultures of S. mutans. There was a synergistic activity in the combination of HypNP and DCD-1 L against S. mutans with an FIC index value of 0.37. The HypNP-DCD-1L-mediated aSDT also displayed the highest cellular uptake and endogenous ROS generation by bacterial cells. When biofilm and persister cells of S. mutans were treated with HypNP-DCD-1 L and subsequently exposed to ultrasound waves, 5.1 log and 3.8 log reductions, respectively, in bacterial numbers were observed (P