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.
Highlights
Drug discovery from natural products focused primarily on plants, but after the discovery and development of penicillin, scientists started looking at natural products from microorganisms [1].Natural products produced by microbes have played a significant role in drug discovery and the treatment of diseases [2], with many of the small molecule drugs launched from 1981 to 2006 derived from microbial natural products [3]
There is a large cadre of antimicrobial drugs available, new antimicrobial drugs are still urgently needed due to increasing drug resistance in pathogenic bacteria [4,5,6,7]
A solitary brown tunicate with striations on the siphons was collected from mangrove roots in the Bastimentos National Park in Bocas del Toro, Panama (Figure S1)
Summary
Drug discovery from natural products focused primarily on plants, but after the discovery and development of penicillin, scientists started looking at natural products from microorganisms [1]. Natural products produced by microbes have played a significant role in drug discovery and the treatment of diseases [2], with many of the small molecule drugs launched from 1981 to 2006 derived from microbial natural products [3]. There is a large cadre of antimicrobial drugs available, new antimicrobial drugs are still urgently needed due to increasing drug resistance in pathogenic bacteria [4,5,6,7]. Mar. Drugs 2017, 15, 250; doi:10.3390/md15080250 www.mdpi.com/journal/marinedrugs.
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