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Vibrio Type III Effector VPA1380 Is Related to the Cysteine Protease Domain of Large Bacterial Toxins

机译:III型弧菌效应子VPA1380与大细菌毒素的半胱氨酸蛋白酶结构域有关

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摘要

Vibrio parahaemolyticus is a Gram-negative halophilic bacterium and one of the leading causes of food-borne gastroenteritis. Its genome harbors two Type III Secretion Systems (T3SS1 and T3SS2), but only T3SS2 is required for enterotoxicity seen in animal models. Effector proteins secreted from T3SS2 have been previously shown to promote colonization of the intestinal epithelium, invasion of host cells, and destruction of the epithelial monolayer. In this study, we identify VPA1380, a T3SS2 effector protein that is toxic when expressed in yeast. Bioinformatic analyses revealed that VPA1380 is highly similar to the inositol hexakisphosphate (IP6)-inducible cysteine protease domains of several large bacterial toxins. Mutations in conserved catalytic residues and residues in the putative IP6-binding pocket abolished toxicity in yeast. Furthermore, VPA1380 was not toxic in IP6 deficient yeast cells. Therefore, our findings suggest that VPA1380 is a cysteine protease that requires IP6 as an activator.
机译:副溶血性弧菌是革兰氏阴性嗜盐细菌,是食源性胃肠炎的主要原因之一。它的基因组包含两个III型分泌系统(T3SS1和T3SS2),但是对于动物模型中的肠毒性,仅需要T3SS2。 T3SS2分泌的效应蛋白先前已显示出可促进肠道上皮的定居,宿主细胞的侵袭和上皮单层的破坏。在这项研究中,我们确定了VPA1380,一种T3SS2效应蛋白,在酵母菌中表达时具有毒性。生物信息学分析表明,VPA1380与几种大型细菌毒素的肌醇六磷酸(IP6)诱导的半胱氨酸蛋白酶结构域高度相似。保守的催化残基和推定的IP6结合口袋中的残基突变消除了酵母中的毒性。此外,VPA1380在IP6缺陷型酵母细胞中无毒。因此,我们的发现表明VPA1380是一种半胱氨酸蛋白酶,需要IP6作为激活剂。

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