State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, China.
PLoS Pathog. 2019 Jul 17;15(7):e1007917. doi: 10.1371/journal.ppat.1007917. eCollection 2019 Jul.
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.
细菌能够协调地将几种效应物递送到宿主细胞中，以干扰感染过程中的细胞进程，这一点很重要，然而，效应物在宿主细胞质溶胶中的精确作用仍有待解决。在这项研究中，我们从致病性爱德华氏菌中鉴定出一种新的细菌毒力效应物，它呈现出与硫氧还蛋白家族成员保守的晶体结构，并被定义为硫氧还蛋白样蛋白（Trxlp）。与经典的细菌硫氧还蛋白不同，Trxlp 可以被转运到宿主细胞中，模拟内源性硫氧还蛋白，从而阻止 ASK1 同型相互作用和磷酸化，然后抑制下游 Erk1/2-和 p38-MAPK 信号级联的磷酸化。此外，Trxlp 介导的 ASK1-Erk/p38-MAPK 轴的抑制促进了斑马鱼幼虫感染模型中爱德华氏菌的发病机制。总之，这些数据为细菌硫氧还蛋白作为一种毒力效应物在下调爱德华氏菌感染过程中的固有免疫反应方面的作用机制提供了新的见解。
