Pagmadulam Baldorj, Tserendulam Dugarsuren, Rentsenkhand Tserennadmid, Igarashi Masayuki, Sawa Ryuichi, Nihei Coh-Ichi, Nishikawa Yoshifumi
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido 080-8555, Japan; Laboratory of Microbial Synthesis, Institute of General and Experimental Biology, Mongolian Academy of Sciences, Ulaanbaatar, Peace avenue-54b, Mongolia.
Laboratory of Microbial Synthesis, Institute of General and Experimental Biology, Mongolian Academy of Sciences, Ulaanbaatar, Peace avenue-54b, Mongolia.
Parasitol Int. 2020 Feb;74:101961. doi: 10.1016/j.parint.2019.101961. Epub 2019 Aug 19.
Natural resources are recognized as important sources of potential drugs for treating various infections, and microorganisms are a rich natural source of diverse compounds. Among the world's microorganisms, actinomycetes, which are abundant in soil and marine, are the well-known producers of a wide range of bioactive secondary metabolites and antibiotics. In the present study, four actinomycetes (samples N25, N6, N18, and N12) were isolated from soil samples in Mongolia. Phylogenetic analysis of these isolates revealed that they share the highest similarity with Streptomyces canus (N25), S. cirratus (N6), S. bacillaris (N18) and S. peucetius (N12), based on 16S rRNA gene sequencing. Crude extracts were obtained from them using ethyl acetate, and the crude fractions were separated by thin layer chromatography. The fractions were then evaluated for their cytotoxicities and their anti-Toxoplasma and antimalarial activities in vitro. The S. canus (N25) crude extract was selected for further chemical characterization based on its antiprotozoal activities. Using liquid chromatography-high resolution mass spectrometry, phenazine-1-carboxylic acid (PCA) was detected and identified in the active fractions of the metabolites from strain N25. We next confirmed that commercially available PCA possesses antiprotozoal activity against T. gondii (IC: 55.5 μg/ml) and Plasmodium falciparum (IC: 6.4 μg/ml) in vitro. The results of this study reveal that soil actinomycetes are potential sources of antiprotozoal compounds, and that PCA merits further investigation as an anti-protozoal agent.
自然资源被认为是治疗各种感染的潜在药物的重要来源,而微生物是多种化合物的丰富天然来源。在世界微生物中,在土壤和海洋中大量存在的放线菌是多种生物活性次生代谢产物和抗生素的著名生产者。在本研究中,从蒙古的土壤样本中分离出了四种放线菌(样本N25、N6、N18和N12)。基于16S rRNA基因测序的系统发育分析表明,这些分离株与犬链霉菌(N25)、卷曲链霉菌(N6)、芽孢链霉菌(N18)和佩鲁茨链霉菌(N12)具有最高的相似性。使用乙酸乙酯从它们中获得粗提物,并通过薄层色谱法分离粗级分。然后评估这些级分在体外的细胞毒性以及它们的抗弓形虫和抗疟活性。基于其抗原虫活性,选择犬链霉菌(N25)粗提物进行进一步的化学表征。使用液相色谱-高分辨率质谱法,在菌株N25代谢产物的活性级分中检测并鉴定出吩嗪-1-羧酸(PCA)。接下来,我们证实市售的PCA在体外对弓形虫(IC:55.5μg/ml)和恶性疟原虫(IC:6.4μg/ml)具有抗原虫活性。本研究结果表明,土壤放线菌是抗原虫化合物的潜在来源,并且PCA作为一种抗原虫剂值得进一步研究。