Pathogenicity and Genomic Analysis of Hypervirulent Aeromonas Hydrophila NN0116 from Nile Tilapia and Head Kidney Transcriptome of Infected Fish Reveals a B-Cell-Dominated Immune Response.

Aeromonas hydrophila is a major pathogen of Motile Aeromonad Septicemia (MAS) in Nile tilapia, with pathogenesis and immunity poorly understood. In early 2026, a > 70% mortality outbreak occurred at a Nanning tilapia farm. The dominant strain NN0116 was identified as A. hydrophila by 16S rRNA and whole-genome ANI analysis. It exhibited high virulence (LD50 = 5.2 × 103 CFU/fish). Its 5.37 Mb genome encodes 5065 proteins and contains T2SS, T3SS, T6SS, and pore-forming toxins. Virulence and antimicrobial resistance genes co-localized on genomic islands GI2 and GI7. The strain was resistant to 12 antibiotic classes but susceptible to third-generation cephalosporins and fluoroquinolones. Head kidney transcriptomics at 24 h identified 1066 differentially expressed genes, including 61 immunoglobulin (Ig) genes. KEGG enrichment revealed 43 significant pathways; the top ten were driven by 26 Ig genes. Network analysis of the top 20 pathways identified B cell receptor signalling (ko04662) and COVID-19 (ko05171) as central nodes, alongside 10 secondary core pathways, all Ig-driven. Integration of bacterial genomic and host transcriptomic data characterizes hypervirulent A. hydrophila NN0116 and demonstrates that Ig-mediated B cell responses are central to host defence, offering targets for vaccines and therapeutics.