Edwardsiella piscicida Type III Secretion System Effector EseK Inhibits Mitogen-Activated Protein Kinase Phosphorylation and Promotes Bacterial Colonization in Zebrafish Larvae

Bacteria utilize type III secretion systems (T3SS) to deliver effectors directly into host cells. Hence, it is very important to identify the functions of bacterial (T3SS) effectors to understand host-pathogen interactions. encodes a functional T3SS effector, EseK, which can be translocated into host cells and affect bacterial loads. Here, it was demonstrated that an mutant (the Δ mutant) significantly increased the phosphorylation levels of p38α, c-Jun NH -terminal kinases (JNK), and extracellular signal-regulated protein kinases 1/2 (ERK1/2) in HeLa cells. Overexpression of EseK directly inhibited mitogen-activated protein kinase (MAPK) signaling pathways in HEK293T cells. The Δ mutant consistently promoted the phosphorylation of MAPKs in zebrafish larva infection models. Further, it was shown that the Δ mutant increased the expression of tumor necrosis factor alpha (TNF-α) in an MAPK-dependent manner. Importantly, the EseK-mediated inhibition of MAPKs attenuated bacterial clearance in larvae. Taken together, this work reveals that the T3SS effector EseK promotes bacterial infection by inhibiting MAPK activation, which provides insights into the molecular pathogenesis of in fish.