从中国棘蛙(Quasipaa spinosa)中分离出的一种前景看好的治疗药物 QS-CATH 的抗菌和免疫调节活性评估

IF 3.9 3区 环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Comparative Biochemistry and Physiology C-toxicology & Pharmacology Pub Date : 2024-05-27 DOI:10.1016/j.cbpc.2024.109943
Wei-Cheng Zheng , Xiao-Yun Cheng , Yu-Hui Tao , Yue-Song Mao , Cheng-Pu Lu , Zhi-Hua Lin , Jie Chen
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引用次数: 0

摘要

在各种脊椎动物中,柔毛鞘氨醇是重要的抗菌肽,是先天免疫系统的重要组成部分。目前,人们对两栖动物柔毛鞘氨醇的了解十分有限,尤其是对其免疫调节作用的了解。为了填补这一知识空白,我们从中国棘蛙(Quasipaa spinosa)的皮肤转录组中获得了猫辣素基因的 cDNA 序列。据预测,Quasipaa spinosa cathelicidin(QS-CATH)的氨基酸序列由一个信号肽、一个cathelin结构域和一个成熟肽组成。将 QS-CATH 氨基酸序列与其他两栖动物的柔毛素氨基酸序列进行比较分析后发现,两栖动物之间功能性成熟肽的变异性很大,而柔毛素结构域则是保守的。QS-CATH 基因在多种组织中表达,其中脾脏的表达水平最高。感染嗜水气单胞菌后,QS-CATH在肾脏、肠道、脾脏、皮肤和肝脏中上调。化学合成的 QS-CATH 对柔性志贺氏菌、金黄色葡萄球菌、大肠杆菌、肠炎沙门氏菌和单核细胞增生李斯特菌具有明显的抗菌活性。此外,QS-CATH 还能破坏柔性志贺氏菌细胞膜的完整性(乳酸脱氢酶释放试验证明了这一点),并能水解柔性志贺氏菌的基因组 DNA。此外,QS-CATH 还能激发 RAW264.7 小鼠白血病单核/巨噬细胞的趋化性,并调节炎症细胞因子基因的表达。这些发现证实了两栖动物柔毛素的抗菌作用及其影响免疫细胞功能的能力。这将加速两栖动物抗菌肽作为治疗药物的潜在利用。
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Assessment of the antimicrobial and immunomodulatory activity of QS-CATH, a promising therapeutic agent isolated from the Chinese spiny frogs (Quasipaa spinosa)

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.

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来源期刊
CiteScore
7.50
自引率
5.10%
发文量
206
审稿时长
30 days
期刊介绍: Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.
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