Comparative genomics of Nocardia seriolae reveals a conserved metabolic core and extensive accessory genome...

Fish nocardiosis is a chronic and economically significant bacterial disease in aquaculture, yet its genomic basis remains poorly resolved beyond single-species studies. It remains unclear whether fish-associated Nocardia share conserved persistence-associated features or exhibit lineage-specific genomic diversification.

We conducted a comparative genomic analysis of 22 Nocardia genomes, including 20 N. seriolae isolates and single representatives of N. salmonicida and N. crassostreae. Genome-wide analyses included phylogenomics, gene-content comparison, pangenome analysis, functional annotation, virulence-associated homolog screening, genomic island detection, and secondary biosynthetic gene cluster prediction.

The conserved genome core was enriched in central metabolism, lipid-associated cell envelope biogenesis, iron acquisition, and stress-response pathways. Virulence-associated homologs were dominated by persistence-associated and metabolic functions, whereas classical toxin systems were limited, although several transport- and secretion-associated homologs were detected, consistent with their potential contribution to host interaction and intracellular persistence. Phylogenomic and gene-content analyses revealed clear species-level divergence but limited host-associated structuring within N. seriolae. Pangenome analysis supported a robust open pangenome structure (γ = 0.386), with extensive accessory gene diversity enriched in regulatory functions, mobile genetic elements, and secondary metabolic pathways. Genomic islands were dominated by insertion-sequence-associated genes, recombinases, regulators, and hypothetical proteins, whereas prophage- and toxin-related signatures were rare. Secondary metabolite analysis revealed extensive biosynthetic diversity, with most biosynthetic gene clusters showing low similarity to characterized reference pathways. However, ectoine- and nocobactin-associated pathways were broadly conserved.

These genome findings are consistent with a persistence-associated pathogenicity model in which fish-associated Nocardia, particularly N. seriolae, may depend more on metabolic resilience, stress adaptation, iron acquisition, and accessory genome plasticity than on classical toxin-mediated virulence. Collectively, the results highlight the importance of accessory genome diversification, iron acquisition, and stress adaptation in shaping host-associated lifestyles and provide a comparative genomic foundation for future functional investigations and aquaculture disease-management strategies.