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

ABSTRACT: Dental caries is driven by acidogenic biofilms dominated by Streptococcus mutans (S. mutans), which create pathological microenvironments through acid production and extracellular polysaccharide matrix formation. 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. These results demonstrate that PBQ's antibacterial mechanism operates through multi-target disruption of essential metabolic networks, creating a "synthetic lethality" effect that overwhelms bacterial homeostatic capacity and constrains resistance development.

ORGANISM(S): Streptococcus mutans

PROVIDER: GSE316134 | GEO | 2026/09/01

REPOSITORIES: GEO