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

機譯：海洋衍生鏈霉菌sp。的抗生素活性的上調和鑒定。通過與人類病原菌的共同培養(yǎng)

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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.
機譯：海洋天然產物藥物的發(fā)現(xiàn)已經開始在疾病治療中發(fā)揮重要作用，最近已批準了幾種藥物。另外，由于放線菌屬的成員，特別是在鏈霉菌屬中，已經發(fā)現(xiàn)了許多微生物天然產物，這是由于它們的代謝多樣性而產生了生物活性的次生代謝產物。但是，許多次生代謝產物無法在實驗室條件下生產，因為燒瓶培養(yǎng)中的生長條件與自然環(huán)境中的條件不同。已經嘗試了各種實驗條件（例如，混合發(fā)酵）以增加先前描述的代謝物的產量，引起先前未檢測到的代謝物的產生，以及增加抗生素活性。成年海生動物（也被稱為被膜動物）是無柄的海洋無脊椎動物，使其容易被捕食，因此被假設使用與宿主相關的細菌，這些細菌會產生具有生物活性的次生代謝產物來進行化學防御。海洋來源的鏈霉菌從巴拿馬的被膜中分離出PTY087I2菌株，然后與人類病原體（包括枯草芽孢桿菌，耐甲氧西林的金黃色葡萄球菌（MSSA），耐甲氧西林的金黃色葡萄球菌（MRSA）和銅綠假單胞菌共培養(yǎng)，然后進行提取。鏈霉菌的共培養(yǎng)。具有這些人類病原體的PTY087I2導致三種抗生素（格拉那汀，格拉莫霉素D和二氫格拉那汀B）以及通過分子網絡發(fā)現(xiàn)的幾種類似物的產生增加。另外，共培養(yǎng)導致針對這些實驗中使用的革蘭氏陽性人類病原體的生物活性大大增強。擴大共培養(yǎng)實驗的利用范圍以實現(xiàn)競爭性相互作用可能會增強代謝產物的產生，并進一步加深我們對這些微生物相互作用的理解。

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