A teleost TFPI-2 peptide that possesses a broad antibacterial spectrum and immune-stimulatory properties
A teleost TFPI-2 peptide that possesses a broad antibacterial spectrum and immune-stimulatory properties
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一种硬骨鱼 TFPI-2 肽，具有广泛的抗菌谱和免疫刺激特性
DOI：
10.1016/j.fsi.2018.08.051
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发表时间：
2018-11-01
影响因子：
4.7
通讯作者：
Zhang, Min
中科院分区：
文献类型：
--
作者：
He, Shu-wen;Wang, Jing-jing;Zhang, Min
组织因子途径抑制物2（TFPI-2）是TFPI-1的类似物，是组织因子（TF）介导的血液凝固的有效内源性抑制剂。先前的报道表明，来自人和脊椎动物的几种肽TFPI-2具有抗多种细菌的抗菌活性。本研究合成了美国红鱼TFPI-2的C端肽TO 24（含24个氨基酸），并对其抗菌谱、作用方式以及免疫刺激特性进行了研究。结果表明，TO 24对革兰氏阳性菌、金黄色葡萄球菌、金黄色葡萄球菌、革兰氏阴性菌、弧菌、弧菌、创伤弧菌和眼斑弧菌、鱼类巨细胞病毒、传染性脾肾坏死病毒（ISKNV）均有较好的抗菌活性。在与创伤弧菌相互作用过程中，TO 24通过破坏细胞膜完整性、穿透细胞质以及诱导基因组DNA和总RNA降解来发挥其抗菌活性。此外，TO 24对红鼓血细胞没有溶血活性。在体外，TO 24增强红鼓巨噬细胞的杀菌活性。在体内，在细菌感染前给予红鼓菌与TO 24显著降低了组织中的病原体传播和复制。这些结果表明，TO 24是一种具有免疫刺激特性的广谱抗菌肽，具有作为水产养殖抗菌剂的潜力。
Tissue factor pathway inhibitor 2 (TFPI-2) is an analogue of TFPI-1 and a potent endogenous inhibitor of tissue factor (TF)-mediated blood coagulation. Previous reports have shown that several peptides derived from human and vertebrates TFPI-2 possess antibacterial activity against diverse bacteria. In this study, a C-terminal peptide, TO24 (with 24 amino acids), derived from red drum (Sciaenops ocellatns) TFPI-2, was synthesized and investigated for its antimicrobial spectrum, action mode, as well as the immune-stimulatory property. Our results indicated that TO24 was active against Gram-positive bacteria Micrococcus luteus and Staphylococcus aureus; Gram-negative bacteria Vibrio litoralis, Vibrio ichthyoenteri, Vibrio vulnificus and Vibrio scophthalmi, as well as fish megalocytivirus, infectious spleen and kidney necrosis virus (ISKNV). During its interaction with V. vulnificus, TO24 exerted its antibacterial activity by destroying cell membrane integrity, penetrating the cytoplasm and inducing degradation of genomic DNA and total RNA. In addition, TO24 had no hemolytic activity against red drum blood cells. In vitro, TO24 enhanced bactericidal activity of red drum macrophages. In vivo, administration of red drum with TO24 before bacterial infection significantly reduced pathogen dissemination and replication in tissues. These results indicate that TO24 is a broad-spectrum antimicrobial peptide with immune-stimulatory properties and it has the potential to be used as an antimicrobial agent in aquaculture.