PUBLICATION

The Edwardsiella piscicida thioredoxin-like protein inhibits ASK1-MAPKs signaling cascades to promote pathogenesis during infection

Authors
Yang, D., Liu, X., Xu, W., Gu, Z., Yang, C., Zhang, L., Tan, J., Zheng, X., Wang, Z., Quan, S., Zhang, Y., Liu, Q.
ID
ZDB-PUB-190719-15
Date
2019
Source
PLoS pathogens   15: e1007917 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Bacterial Proteins/chemistry
  • Bacterial Proteins/genetics
  • Bacterial Proteins/metabolism*
  • Crystallography, X-Ray
  • Edwardsiella/immunology
  • Edwardsiella/metabolism
  • Edwardsiella/pathogenicity*
  • Enterobacteriaceae Infections/etiology*
  • Enterobacteriaceae Infections/metabolism
  • Enterobacteriaceae Infections/microbiology
  • HeLa Cells
  • Host Microbial Interactions/immunology
  • Humans
  • Immunity, Innate
  • MAP Kinase Kinase Kinase 5/metabolism*
  • MAP Kinase Signaling System
  • Models, Molecular
  • Signal Transduction
  • Thioredoxins/chemistry
  • Thioredoxins/genetics
  • Thioredoxins/metabolism*
  • Virulence
  • Virulence Factors/chemistry
  • Virulence Factors/genetics
  • Virulence Factors/metabolism
PubMed
31314784 Full text @ PLoS Pathog.
Abstract
It is important that bacterium can coordinately deliver several effectors into host cells to disturb the cellular progress during infection, however, the precise role of effectors in host cell cytosol remains to be resolved. In this study, we identified a new bacterial virulence effector from pathogenic Edwardsiella piscicida, which presents conserved crystal structure to thioredoxin family members and is defined as a thioredoxin-like protein (Trxlp). Unlike the classical bacterial thioredoxins, Trxlp can be translocated into host cells, mimicking endogenous thioredoxin to abrogate ASK1 homophilic interaction and phosphorylation, then suppressing the phosphorylation of downstream Erk1/2- and p38-MAPK signaling cascades. Moreover, Trxlp-mediated inhibition of ASK1-Erk/p38-MAPK axis promotes the pathogenesis of E. piscicida in zebrafish larvae infection model. Taken together, these data provide insights into the mechanism underlying the bacterial thioredoxin as a virulence effector in downmodulating the innate immune responses during E. piscicida infection.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping