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Mar. Drugs 2017, 15(8), 250; doi:10.3390/md15080250

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

Division of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA
These authors contributed equally to this work.
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Received: 1 June 2017 / Revised: 31 July 2017 / Accepted: 2 August 2017 / Published: 11 August 2017
(This article belongs to the Special Issue Connecting Marine Microbial Natural Products to Biosynthetic Pathways)
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Abstract

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. View Full-Text
Keywords: mixed fermentation; co-culture with human pathogens; microbial natural product drug discovery; antibiotic secondary metabolites mixed fermentation; co-culture with human pathogens; microbial natural product drug discovery; antibiotic secondary metabolites
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sung, A.A.; Gromek, S.M.; Balunas, M.J. Upregulation and Identification of Antibiotic Activity of a Marine-Derived Streptomyces sp. via Co-Cultures with Human Pathogens. Mar. Drugs 2017, 15, 250.

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