Upregulation and Identification of Antibiotic Activity of a Marine-Derived Streptomyces sp. via Co-Cultures with Human Pathogens.

Upregulation and Identification of Antibiotic Activity of a Marine-Derived Streptomyces sp. via Co-Cultures with Human Pathogens.
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海洋衍生链霉菌属的抗生素活性的上调和鉴定。通过与人类病原体的共同培养。

DOI:
10.3390/md15080250
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发表时间:
2017-08-11
期刊:
影响因子:
5.4
通讯作者:
Balunas MJ
Balunas MJ
中科院分区:
医学2区
文献类型:
--
作者:
Sung AA;Gromek SM;Balunas MJ

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海洋天然产物药物发现已开始在疾病治疗中发挥重要作用,最近批准了几种药物。此外,已经从放线菌目的成员,特别是链霉菌属中发现了许多微生物天然产物,这是由于它们产生生物活性次级代谢产物的代谢多样性。然而,许多次级代谢产物不能在实验室条件下产生,因为烧瓶培养中的生长条件与自然环境中的条件不同。各种实验条件(例如,混合发酵)已经尝试增加先前描述的代谢物的产率,引起先前未检测到的代谢物的产生,并增加抗生素活性。成年海鞘-也被称为被囊动物-是固着的海洋无脊椎动物,使它们容易被捕食,因此假设使用宿主相关的细菌,产生生物活性的次级代谢产物进行化学防御。从巴拿马被囊动物中分离得到一株海洋来源的链霉菌PTY 087 I2,并将其与枯草芽孢杆菌、甲氧西林敏感金黄色葡萄球菌(MSSA)、耐甲氧西林金黄色葡萄球菌(MRSA)和铜绿假单胞菌共培养,然后进行提取。将链霉菌PTY 087 I2与这些人类病原体中的每一种共培养,导致三种抗生素的产量增加:石榴素、石榴霉素D和二氢石榴素B,以及通过分子网络观察到的几种类似物。此外,共培养物导致针对这些实验中使用的革兰氏阳性人类病原体的生物活性强烈增强。扩大利用共培养实验,以允许竞争性的相互作用,可以提高代谢产物的生产和进一步了解这些微生物的相互作用。
Marine natural product drug discovery has begun to play an important role in the treatment of disease, with several recently approved drugs. In addition, numerous microbial natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces, due to their metabolic diversity for production of biologically active secondary metabolites. However, many secondary metabolites cannot be produced under laboratory conditions because growth conditions in flask culture differ from conditions in the natural environment. Various experimental conditions (e.g., mixed fermentation) have been attempted to increase yields of previously described metabolites, cause production of previously undetected metabolites, and increase antibiotic activity. Adult ascidians—also known as tunicates—are sessile marine invertebrates, making them vulnerable to predation and therefore are hypothesized to use host-associated bacteria that produce biologically active secondary metabolites for chemical defense. A marine-derived Streptomyces sp. strain PTY087I2 was isolated from a Panamanian tunicate and subsequently co-cultured with human pathogens including Bacillus subtilis, methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa, followed by extraction. Co-culture of Streptomyces sp. PTY087I2 with each of these human pathogens resulted in increased production of three antibiotics: granaticin, granatomycin D, and dihydrogranaticin B, as well as several analogues seen via molecular networking. In addition, co-cultures resulted in strongly enhanced biological activity against the Gram positive human pathogens used in these experiments. Expanded utilization of co-culture experiments to allow for competitive interactions may enhance metabolite production and further our understanding of these microbial interactions.
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发表时间: 2007-04-01
影响因子: 5.1
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