As a severe emerging shrimp disease, TPD has heavily impacted the shrimp aquaculture industry and resulted in serious economic losses in China since spring 2020. This study aimed to identify the key virulent factors and related genes of the , for a better understanding of its pathogenicity of the novel highly lethal infectious pathogen, as well as its molecular epidemiological characteristics in China. The present study revealed that a novel protein, high virulent protein-2 (MW >100 kDa), is responsible to the lethal virulence of to shrimp post-larvae. The results are essential for effectively diagnosing and monitoring novel pathogenic bacteria, like , in aquaculture shrimps and would be beneficial to the fisheries department in early warning of emergence and developing prevention strategies to reduce economic losses due to severe outbreaks of TPD. Elucidation of the key virulence genes and genomics of could also provide valuable information on the evolution and ecology of this emerging pathogen in aquaculture environments.