PDF(Pubmed)
Abstract：
[Cu(NN1)2]ClO4 is a copper (I) complex, where NN1 is an imine ligand 6-((quinolin-2-ylmethylene) amino)-2H-chromen-2-one obtained by derivatization of natural compound coumarin, developed for the treatment of infectious diseases that affect salmonids. In previous research, we showed that the Cu(I) coordination complex possesses antibacterial activity against Flavobacterium psychrophilum, providing protection against this pathogen in rainbow trout during challenge assays (with an RPS of 50%). In the present study, the effects of administering [Cu(NN1)2]ClO4 to Oncorhynchus mykiss over a 60-days period were evaluated with regard to systemic immune response and its potential to alter intestinal microbiota composition. In O. mykiss, an immunostimulatory effect was evident at days 30 and 45 after administration, resulting in an increment of transcript levels of IFN-γ, IL-12, TNF-α, lysozyme and perforin. To determine whether these immunomodulatory effects correlated with changes in the intestinal microbiota, we analyzed the metagenome diversity by V4 16S rRNA sequencing. In O. mykiss, both [Cu(NN1)2]ClO4 and commercial antibiotic florfenicol had comparable effects at the phylum level, resulting in a predominance of proteobacteria and firmicutes. Nonetheless, at the genus level, florfenicol and [Cu(NN1)2]ClO4 complex exhibited distinct effects on the intestinal microbiota of O. mykiss. In conclusion, our findings demonstrate that [Cu(NN1)2]ClO4 is capable of stimulating the immune system at a systemic level, while inducing alterations in the composition of the intestinal microbiota in O. mykiss.
摘要：
[Cu(NN1)2]ClO4是一种铜(I)配合物,其中NN1是通过衍生天然化合物香豆素获得的亚胺配体6-（（喹啉-2-基亚甲基）氨基）-2H-色烯-2-酮，开发用于治疗影响鲑鱼的传染病。在以前的研究中，我们表明，Cu（I）配位复合物对嗜冷黄杆菌具有抗菌活性，在攻击测定过程中对虹鳟鱼中的这种病原体提供保护（RPS为50％）。在本研究中,评估了在60天内对Oncorhynchusmykiss施用[Cu（NN1）2]ClO4对全身免疫反应及其改变肠道微生物群组成的潜力的影响。在O.mykiss中，在给药后30和45天，免疫刺激作用是明显的，导致IFN-γ的转录水平增加，IL-12,TNF-α,溶菌酶和穿孔素。为了确定这些免疫调节作用是否与肠道微生物群的变化相关，我们通过V416SrRNA测序分析了宏基因组多样性。在O.mykiss中，[Cu（NN1）2]ClO4和商业抗生素氟苯尼考在门水平上具有相当的效果，导致蛋白质和铁质的优势。尽管如此，在属一级，氟苯尼考和[Cu（NN1）2]ClO4复合物对O.mykiss的肠道菌群表现出明显的影响。总之,我们的研究结果表明，[Cu（NN1）2]ClO4能够在系统水平上刺激免疫系统，同时诱导O.mykiss中肠道微生物群的组成发生变化。
