ZFIN ID: ZDB-PUB-180711-1
Edwardsiella piscicida T3SS effector EseK inhibits MAPKs phosphorylation and promotes bacterial colonization in zebrafish larvae
Cao, H., Han, F., Tan, J., Hou, M., Zhang, Y., Yang, D., Liu, Q.
Date: 2018
Source: Infection and Immunity   86(9): (Journal)
Registered Authors: Liu, Qin
Keywords: none
MeSH Terms:
  • Animals
  • Edwardsiella
  • Enterobacteriaceae Infections/enzymology*
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Larva/microbiology
  • Mitogen-Activated Protein Kinases/antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases/metabolism
  • Mutation
  • Phosphorylation
  • Signal Transduction
  • Tumor Necrosis Factor-alpha/genetics
  • Tumor Necrosis Factor-alpha/metabolism
  • Type III Secretion Systems/genetics
  • Type III Secretion Systems/metabolism*
  • Zebrafish/microbiology*
PubMed: 29986890 Full text @ Infect. Immun.
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. Edwardsiella piscicida encodes a functional T3SS effector, EseK, which can be translocated into host cells and affect bacterial loads. Here, it was demonstrated that an eseK mutant (the ΔeseK mutant) significantly increased the phosphorylation levels of p38α, c-Jun NH2-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 ΔeseK mutant consistently promoted the phosphorylation of MAPKs in zebrafish larva infection models. Further, it was shown that the ΔeseK mutant increased the expression of tumor necrosis factor alpha (TNF-α) in an MAPK-dependent manner. Importantly, the EseK-mediated inhibition of MAPKs in vivo attenuated bacterial clearance in larvae. Taken together, this work reveals that the E. piscicida T3SS effector EseK promotes bacterial infection by inhibiting MAPK activation, which provides insights into the molecular pathogenesis of E. piscicida in fish.