| Summary: | The rise in drug resistance coupled with the virtual halt in the antibacterial drug pipeline has lead once highly treatable bacterial infections back to the brink of epidemic levels. The need for novel antibiotic agents is urgent. An important route for the discovery of novel therapeutics continues to be the screening of microbial natural products. However, the discovery rate of novel molecules from terrestrial and near-shore environments is decreasing. Turning to largely unexplored habitats is a necessary direction for the search of novel biological and chemical diversity. One of the greatest resources yet to be explored is the microbial life in the deep subsurface ocean sediments. The overall aim of this dissertation is to better understand the biogeography and community structure of deep subseafloor microorganisms to accelerate the discovery of novel diversity and bioactive natural products. Culture-independent and culture-dependent strategies were used to investigate the microbial biodiversity and biomedical potential of deep subseafloor sediments from two unique environments. The opening study reported in chapter two represents the first investigation of the microbial diversity in the deep subsurface sediments underlying the ice-covered central Arctic Ocean. Sediment samples were collected during the Integrated Ocean Drilling Program (IODP) Arctic Coring Expedition (Expedition 302). The drill site was located ∼250 km from the North Pole on the Lomonosov Ridge in a water depth of 1209 m. Culture-independent methods were used to characterize the bacterial and archaeal communities in the three geochemical environments (an upper ammonium oxidation zone, a carbonate dissolution zone and a deep sulfate reduction zone) identified in the 428 m sediment stack. Bacterial 16S rRNA genes were successfully amplified from each of the biogeochemical zones, while archaea was only amplified from the deep sulfate reduction zone. The microbial communities at each zone are phylogenetically distinct and are most closely related to those from other similar deep subsurface environments. The second study, presented in chapter three, on microbial communities in the deep subsurface focuses on the biodiversity of actinomycete, especially Salinispora, in the South Pacific Gyre. Actinomycetes are proven prolific producers of bioactive natural products. During a coring expedition to the South Pacific Gyre, deep sea (>3600 m) sedimentary core samples were collected from sediments extending to 7 meters beneath seafloor (mbsf). The slow sedimentation rates and resulting oxic, oligotrophic sediments of the South Pacific Gyre make this environment unlike any previously studied. Culture independent methods were used to probe the sediments for actinomycete and Salinispora biodiversity. Actinomycete and Salinispora 16S rRNA genes were amplified from 55% and 49% of samples, respectively, and analyzed in a biogeographical context. This study expands the biogeographical range of this biosynthetically potent group of bacteria to include subsurface sediments underlying low productivity surface waters in the open ocean. Reported in chapter four, the final study aims to culture novel microbes from deep sediments and evaluate them for antibiotic activity. A full IODP drilling expedition (Expedition 329) returned to the same South Pacific Gyre sites investigated in the previous study to examine the entire sediment stack. The depth of the sediments ranges from 75 m on the outer edges of the gyre to only 15 m in the heart of the gyre. To date, 150 bacterial and 120 fungal isolates have been cultivated from the subsurface sediments using standard laboratory conditions. A remarkable 60% of bacterial and 80% of fungal isolates have demonstrated antibacterial activity against one or more bacterial test strains. In addition, inhibition of bioluminescence in Vibrio harveyi , a quorum sensing controlled phenotype, was observed by 46% of the bacterial isolates tested. Inhibitors of bacterial quorum sensing represent potentially novel therapeutics for the treatment of bacterial infections. Clearly, deep subsurface sediments, even those underlying the highly unproductive waters of the oceans' major gyres, represent an immense source of untapped biomedical potential.
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