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海藻相关的异养细菌:有前景的抗感染和抗癌药物的新范例。

Seaweed-associated heterotrophic bacteria: new paradigm of prospective anti-infective and anticancer agents.

机构信息

Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, India.

Faculty of Marine Sciences, Lakeside Campus, Cochin University of Science and Technology, Cochin, Kerala State, India.

出版信息

Arch Microbiol. 2021 Apr;203(3):1241-1250. doi: 10.1007/s00203-020-02106-4. Epub 2020 Nov 2.

Abstract

Ever since the development of the first antibiotic compound with anticancer potential, researchers focused on isolation and characterization of prospective microbial natural products with potential anti-infective and anticancer activities. The present work describes the production of bioactive metabolites by heterotrophic bacteria associated with intertidal seaweeds with potential anti-infective and anticancer activities. The bacteria were isolated in a culture-dependent method and were identified as Shewanella algae MTCC 12715 (KX272635) and Bacillus amyloliquefaciens MTCC 12716 (KX272634) based on combined phenotypic and genotypic methods. Further, the bacteria were screened for their ability to inhibit drug-resistant infectious pathogens and prevent cell proliferation of human liver carcinoma (HepG2) and breast cancer (MCF7) cell lines, without affecting the normal cells. Significant anti-infective activity was observed with bacterial cells and their organic extracts against broad-spectrum multidrug-resistant pathogens, such as vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Klebsiella pneumonia and Pseudomonas aeruginosa with minimum inhibitory concentration ≤ 3.0 µg mL as compared to the antibiotic agents' chloramphenicol and ampicillin, which were active at ≥ 6.25 mg mL. The extracts also exhibited anticancer activity in a dose-responsive pattern against HepG2 (with IC, half maximal inhibitory concentration ~ 78-83 µg mL) and MCF7 (IC ~ 45-48 µg mL) on tetrazolium bromide screening assay with lesser cytotoxic effects on normal fibroblast (L929) cell lines (IC > 100 µg mL). The results revealed that seaweed-associated heterotrophic bacteria could occupy a predominant role for a paradigm shift towards the development of prospective anti-infective and anticancer agents.

摘要

自从开发出第一个具有抗癌潜力的抗生素化合物以来,研究人员一直专注于分离和表征具有潜在抗感染和抗癌活性的微生物天然产物。本工作描述了具有潜在抗感染和抗癌活性的潮间带海藻伴生异养细菌产生生物活性代谢物的情况。采用依赖培养的方法分离细菌,并基于表型和基因型综合方法将其鉴定为栖海拉氏菌 MTCC 12715(KX272635)和解淀粉芽孢杆菌 MTCC 12716(KX272634)。进一步,筛选了细菌抑制耐药性感染性病原体和阻止人肝癌(HepG2)和乳腺癌(MCF7)细胞系增殖的能力,而不影响正常细胞。细菌细胞及其有机提取物对广谱多药耐药病原体(如万古霉素耐药粪肠球菌、耐甲氧西林金黄色葡萄球菌、肺炎克雷伯菌和铜绿假单胞菌)具有显著的抗感染活性,最低抑菌浓度≤3.0μgmL,而抗生素药物氯霉素和氨苄西林的活性为≥6.25mgmL。提取物在噻唑蓝筛选试验中还表现出剂量依赖性的抗癌活性,对 HepG2(IC5078-83μgmL)和 MCF7(IC5045-48μgmL),对正常成纤维细胞(L929)细胞系的细胞毒性作用较小(IC>100μgmL)。结果表明,海藻伴生异养细菌可能在开发潜在抗感染和抗癌药物方面发挥主导作用,从而实现范式转变。

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