Edwardsiella tarda is an Enterobacteriaceae (Leung et al., 2019) a common pathogen of fish that is widely distributed in freshwater and marine (Park et al., 2012). Edwardsiella tarda, which cause edwardsiellosis in fish, and E. tarda is a zoonotic agent that could causes acute gastroenteritis in humans (Bockemühl et al., 1971). Edwardsiella piscicida is the member of Edwardsiella family, which is closely related with E. tarda and can also infect human and other animals by the food chain (Vayssier-Taussat et al., 2014). Edwardsiella could cause skin and soft tissue infection to human by the aquatic-based infections (Vasagar et al., 2018). Edwardsiella tarda is commonly associated with systemic disease and could cause outbreaks disease in fish. Edwardsiella tarda caused Lates calcarifer erythema and/or on the ventrum and gastrointestine tract, haemorrhage on the fin/ oral and wall at necropsy, gill pallor (Loch et al., 2017). Nowadays, E. tarda as a zoonotic bacteria control is an urgent task with the scale of aquaculture expanding. Antibiotics are still the main treatment for bacterial infections (Dong et al., 2018). But antibiotic-resistant pathogens have increased due to the irregular use and abuse of antibiotics (Moreno et al., 2006).The toll like receptor (TLR) 4 is the first member of the TLR family to be identified as a pattern recognition receptor pathogen. TLR4 signals are involved in the innate immune responses of most microorganisms, including gram bacteria, mycobacteria, spirochetes, yeasts, and some viruses (e. g. human respiratory syncytial virus and breast tumour viruses) (Spanou et al., 2017). TLR2 is known for a receptor that can recognize multiple bacterial and fungal cell wall