MARTX toxin of Vibrio vulnificus induces RBC phosphatidylserine exposure that can contribute to thrombosis
Han Young Chung,
Yiying Bian,
Kyung-Min Lim,
Byoung Sik Kim and
Sang Ho Choi ()
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Han Young Chung: Seoul National University
Yiying Bian: China Medical University
Kyung-Min Lim: Ewha Womans University
Byoung Sik Kim: Ewha Womans University
Sang Ho Choi: Seoul National University
Nature Communications, 2022, vol. 13, issue 1, 1-12
Abstract:
Abstract 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 Ca2+ 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.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32599-0
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DOI: 10.1038/s41467-022-32599-0
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