Screening for Antimycobacterial Activity of Actinomycetes Collected in Vietnam – Isolation and Activity of Metabolites from Streptomyces alboniger (A121)

Ni Thi Ngoc Huynh, Ninh Thi Pham, Chien Van Tran, Dung Thi Nguyen, Mai Thi Ngoc Dinh, Van Thi Nguyen, Minh Hong Nguyen, Hieu Van Ngo, Anh Ngoc Ho, Jinhua Cheng, Joo-Won Suh, Sung Van Tran, Thao Kim Nu Nguyen, Thao Thi Phuong Tran
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Abstract

Actinomycetes have been known to be the great natural sources to explore antibiotics for the treatment of tuberculosis (TB). The isolation of actinomycetes from the samples in Vietnam followed by the screening of their antimycobacterial activity was performed in this study. The metabolites isolated from the most active strain were further evaluated for their antimycobacterial, antimicrobial and cytotoxic activity. Actinomycetes were growth in culture media, isolated and identified by colony, spore chain morphology and 16S rRNA gene sequencing. Agar diffusion assay was used for the screening of the isolated strains against Mycobacterium smegmatis, a safety surrogate for Mycobacterium tuberculosis. The metabolites produced from the most active strain were investigated by actinomycete fermentation, extraction and isolation from biomass and cultures. The structures of the isolated compound were elucidated by spectral data and comparison with the reported literatures. 181 strains were isolated from nine regions along the north to central Vietnam. The five most active strains against Mycobacterium smegmatis were detected. Following the bioassay-guided result, the strain A121 ( Streptomyces alboniger) was selected for further isolation of the bioactive metabolites. As a result, obscurolide B2β (1) and chartreusin (2) were obtained and evaluated for their antimycobacterial activity against M. smegmatis. Compound 2 displayed potential antimycobacterial activity, antimicrobial effect against the Gram positive bacteria Staphylococcus aureus, Bacillus subtilis, Lactobacillus fermentum and cytotoxicity against four cancer cell lines KB, HepG-2, Lu-1 and MCF-7. Five strains possessing potential antimycobacterial activity were identified from the samples collected in Vietnam. Two compounds including obscurolide B2β (1) and chartreusin (2) were isolated from the most active strain A121 ( Streptomyces alboniger). This is the first time these compounds have been isolated from this strain. Chartreusin (2) exhibited notable antimycobacterial, antimicrobial and cytotoxic activity, making its worthy attention for further drug development, particularly for antituberculosis therapeutic agents.
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越南采集的放线菌的抗霉菌活性筛选--从 Streptomyces alboniger(A121)中分离出的代谢物及其活性
众所周知,放线菌是探索治疗结核病(TB)抗生素的重要天然来源。本研究从越南的样本中分离出放线菌,并对其抗结核活性进行了筛选。从活性最强的菌株中分离出的代谢物进一步评估了它们的抗霉菌、抗微生物和细胞毒性活性。放线菌在培养基中生长,通过菌落、孢子链形态和 16S rRNA 基因测序进行分离和鉴定。琼脂扩散试验用于筛选分离出来的菌株对烟肉分枝杆菌(结核分枝杆菌的安全代用品)的抗性。通过放线菌发酵、从生物质和培养物中提取和分离,对最活跃菌株产生的代谢物进行了研究。通过光谱数据和与文献报道的比较,阐明了分离化合物的结构。从越南北部到中部的 9 个地区分离出 181 株菌株。检测出了对分枝杆菌最有效的五种菌株。根据生物测定指导结果,选择了 A121 菌株(白链霉菌)进一步分离生物活性代谢物。结果获得了遮盖苷 B2β(1)和海藻糖苷(2),并评估了它们对烟曲霉的抗霉菌活性。化合物 2 具有潜在的抗霉菌活性,对革兰氏阳性菌金黄色葡萄球菌、枯草芽孢杆菌、发酵乳杆菌具有抗菌作用,对四种癌细胞株 KB、HepG-2、Lu-1 和 MCF-7 具有细胞毒性。从越南采集的样本中鉴定出五株具有潜在抗霉菌活性的菌株。从活性最强的菌株 A121(白链霉菌)中分离出了两种化合物,包括淫羊藿苷 B2β (1) 和石杉碱 (2)。这是首次从该菌株中分离出这些化合物。Chartreusin (2) 具有显著的抗霉菌、抗微生物和细胞毒性活性,值得进一步开发,尤其是作为抗结核治疗药物。
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