Transcriptomic profiling of Streptococcus mutans treated with pH-responsive PAMAM-pHly-1@batimastat+quercetin nanoparticles

We engineered a pH-responsive multifunctional nanoplatform, PAMAM-pHly-1@batimastat+quercetin (PBQ), designed to achieve coordinated biofilm control, collagen matrix preservation, and dentin remineralization. This system leverages a generation-5 PAMAM dendrimer core conjugated with pH-sensitive antimicrobial peptide pHly-1 and loaded with batimastat and quercetin.

To elucidate the molecular mechanisms underlying PBQ's antimicrobial efficacy, we performed RNA sequencing analysis of S. mutans treated with PBQ at pH 5.5, which mimics the acidic cariogenic microenvironment. Transcriptomic profiling revealed that PBQ systematically disrupts bacterial virulence through coordinated suppression of multiple interdependent pathways. Key findings include significant downregulation of biofilm formation genes involved in glycogen biosynthesis and glucan biosynthesis, disruption of carbohydrate metabolism, impairment of transmembrane transport systems, and suppression of arginine metabolism.