Abstract

Nocardia seriolae(N. seriolae) is a significant bacterial pathogen in global aquaculture, causing substantial economic losses. Live-attenuated vaccines represent a promising control strategy, but their molecular mechanisms remain poorly understood. This study employed a quantitative proteomic approach to compare the proteomic profiles of a virulent wild-type strain (F1) and an attenuated vaccine strain (F110) ofN. seriolae. Using a data-independent acquisition (DIA)-based LC-MS/MS analysis, we identified 4516 proteins, with 540 showing significant differential expression (311 upregulated, 229 downregulated). Bioinformatic analysis revealed that upregulated proteins in F110 were primarily involved in metabolic processes, including phosphatidate cytidylyltransferase and various enzymes related to amino acid and nucleotide metabolism. Conversely, downregulated proteins were enriched in virulence-associated functions, including HtpX and MFS transporter permease. These findings suggest that attenuation involves a complex reprogramming of metabolic pathways coupled with a reduction in key virulence factors, providing insights into the potential molecular basis of vaccine development and potential targets for novel therapeutic strategies.