National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, Seoul National University, Seoul, 08826, Republic of Korea.
Center for Food and Bioconvergence, Seoul National University, Seoul, 08826, Republic of Korea.
Nat Commun. 2022 Aug 17;13(1):4846. doi: 10.1038/s41467-022-32599-0.
V. vulnificus-infected patients suffer from hemolytic anemia and circulatory lesions, often accompanied by venous thrombosis. However, the pathophysiological mechanism of venous thrombosis associated with V. vulnificus infection remains largely unknown. Herein, V. vulnificus infection at the sub-hemolytic level induced shape change of human red blood cells (RBCs) accompanied by phosphatidylserine exposure, and microvesicle generation, leading to the procoagulant activation of RBCs and ultimately, acquisition of prothrombotic activity. Of note, V. vulnificus exposed to RBCs substantially upregulated the rtxA gene encoding multifunctional autoprocessing repeats-in-toxin (MARTX) toxin. Mutant studies showed that V. vulnificus-induced RBC procoagulant activity was due to the pore forming region of the MARTX toxin causing intracellular Ca influx in RBCs. In a rat venous thrombosis model triggered by tissue factor and stasis, the V. vulnificus wild type increased thrombosis while the ΔrtxA mutant failed to increase thrombosis, confirming that V. vulnificus induces thrombosis through the procoagulant activation of RBCs via the mediation of the MARTX toxin.
创伤弧菌感染患者患有溶血性贫血和循环损伤，常伴有静脉血栓形成。然而，创伤弧菌感染相关静脉血栓形成的病理生理机制在很大程度上尚不清楚。在此，亚溶血性水平的创伤弧菌感染诱导人红细胞（RBC）形态改变，伴随磷脂酰丝氨酸暴露和微囊泡生成，导致 RBC 的促凝激活，最终获得促血栓形成活性。值得注意的是，暴露于 RBC 的创伤弧菌大量上调编码多功能自加工重复毒素（MARTX）毒素的 rtxA 基因。突变研究表明，创伤弧菌诱导的 RBC 促凝活性是由于 MARTX 毒素的孔形成区域导致 RBC 内 Ca 内流。在组织因子和停滞触发的大鼠静脉血栓形成模型中，野生型创伤弧菌增加血栓形成，而 ΔrtxA 突变体则不能增加血栓形成，证实创伤弧菌通过 MARTX 毒素介导的 RBC 促凝激活诱导血栓形成。
