The dominant strain was isolated from the diseased fish in this study to investigate the cause of the disease outbreak of Odontobutis potamophilus in a farm in Changshu in March 2021.The dominant bacterium was identified by morphological observation,physicochemical characterization and gyrB gene homology analysis.The pathogenicity of the isolates was determined by artificial infection test,histopathological observation,virulence factor,and virulence gene detection,and the drug resistance and immune-related gene expression changes of the isolates were determined after infection.The results showed that the pathogen causing the mass death of Odontobutis potamophilus was Aeromonas salmonicida(OM203113).The LD50 of the representative strain G2-4-1 to Odontobutis potamophilus was 1.8×106 CFU/mL.Infection with the pathogenic bacteria in Odontobutis potamophilus can cause obvious degeneration,necrosis and inflammatory cell infiltration in the liver,spleen,kidney and gill tissues.The strain carries aer,hly,exu and other virulence genes,and has protease,lecithinase,amylase,li-pase,gelatinase and hemolysin activities but does not have DNase activity.The drug resistance analysis showed that the isolate G2-4-1 was resistant to 8 drugs including penicillin G,ampicillin,and oxacillin,2 drugs inter-mediary to clarithromycin and spectinomycin,sensitive to 24 drugs such as enrofloxacin,florfenicol.Immune-related gene expression analysis showed that MHCⅡB,MyD88,TLR and SOD were significantly up-regula-ted in gill,spleen and head kidney tissues at the early stage of infection.It provides a scientific basis for the pre-vention,control,and treatment of bacterial disease of A.salmonicida.