Synthesis of Berberine-Loaded Carbon Dots and Their Antimicrobial Mechanism Against <i>Metschnikowia bicuspidata</i> : Insights from Transcriptomic Analysis

Pathogenic microorganisms, such as <i>Metschnikowia bicuspidata</i>, cause significant issues for the sustainable development of aquaculture. While natural antimicrobial agents show promise, their stability and target range are limited. For instance, berberine exhibits antibacterial activity by inhibiting ergosterol synthesis in fungi and inducing ROS production, but its poor solubility and low membrane penetration hinder its application. Carbon dots (CDs), with high surface area, tunable chemistry, and good biocompatibility, offer unique advantages for drug delivery. This study synthesized berberine CDs (B-CDs) and evaluated their antibacterial activity against <i>M. bicuspidata</i>. B-CDs were prepared via hydrothermal synthesis and exhibited excellent nanostructures, dispersibility, and biocompatibility. The minimum inhibitory concentration of B-CDs was 0.031 mg/mL, lower than berberine alone (1 mg/mL). Transcriptomic analysis revealed that B-CDs disrupted energy metabolism by downregulating key glycolytic enzymes. Gene ontology and KEGG enrichment analyses indicated that differentially expressed genes were involved in carbohydrate metabolism and signaling pathways. In conclusion, B-CDs improve solubility, cellular uptake, and ROS generation, enhancing antibacterial effects. This nanomaterial shows promise for sustainable pathogen control in aquaculture.